☆ 4.8 Review

Immunometabolic reprogramming, another cancer hallmark

FRONTIERS IN IMMUNOLOGY (2023)

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Review Oncology

Thermal immuno-nanomedicine in cancer

Zhe Yang et al.

Summary: Immunotherapy has revolutionized cancer treatment, but promoting antitumour immunity in patients with resistant tumours remains a challenge. Thermal therapies offer a promising approach by reprogramming the tumour microenvironment and promoting immune cell recruitment. This review summarizes the role of thermal therapies in combination with immunotherapies, as well as the development of thermal immuno-nanomedicines for cancer treatment.

NATURE REVIEWS CLINICAL ONCOLOGY (2023)

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Review Endocrinology & Metabolism

Metabolic determinants of tumour initiation

Julia S. Brunner et al.

Summary: This review emphasizes the important role of metabolic pathways in influencing the early stages of tumor development, highlighting the metabolic alterations present in cancer cells compared to normal cells. It discusses how these metabolic changes can support the growth and survival of tumors, as well as their potential impact on gene expression programs that promote malignant progression. The review also explores the factors, both intrinsic and extrinsic, that contribute to tumor initiation and underscores the significance of understanding how metabolic pathways control this process in the design of interventions to limit tumor incidence.

NATURE REVIEWS ENDOCRINOLOGY (2023)

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Article Chemistry, Multidisciplinary

NADPH Selective Depletion Nanomedicine-Mediated Radio-Immunometabolism Regulation for Strengthening Anti-PDL1 Therapy against TNBC

Ying Wang et al.

Summary: A multifunctional drug-like copolymer has been synthesized to develop a nanomedicine targeting hypoxia and loaded with BMS202 for anti-PD-L1 therapy against TNBC. This innovative approach combines anti-PD-L1 therapy with low-dose radiotherapy to upregulate tumor PD-L1 expression and reprogram the immunometabolism of the tumor microenvironment, providing a promising strategy to reinforce the efficacy of anti-PD-L1 therapy against TNBC.

ADVANCED SCIENCE (2023)

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Article Oncology

T lymphocytes induce human cancer cells derived from solid malignant tumors to secrete galectin-9 which facilitates immunosuppression in cooperation with other immune checkpoint proteins

Stephanie Schlichtner et al.

Summary: This study revealed that T lymphocytes can induce the secretion of galectin-9 in human cancer cells derived from solid malignant tumors, which exhibits higher immunosuppressive activity. This finding is of great significance for immunotherapy in cancer treatment.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

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Review Immunology

Roles of natural killer cells in immunity to cancer, and applications to immunotherapy

Natalie K. Wolf et al.

Summary: This review explains the role of natural killer (NK) cells in promoting immunity to tumors and discusses various therapeutic approaches being developed for cancer patients. Recent advances have improved our understanding of NK cells in tumor and viral immunity, showcasing their potential for immunotherapy for cancer.

NATURE REVIEWS IMMUNOLOGY (2023)

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Editorial Material Oncology

Whole-genome sequencing of East Asian lung cancers reveals new germline pathogenic variants

Semanti Mukherjee et al.

Summary: In this study, Wang et al. used whole-genome sequencing to comprehensively analyze common and rare variants associated with lung cancer risk in individuals with East Asian ancestry. Their findings suggest that rare promoter variants in the BRCA2 gene are associated with an increased risk of lung cancer.

CANCER CELL (2022)

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Article Chemistry, Multidisciplinary

Coordination Polymer-Coated CaCO3 Reinforces Radiotherapy by Reprogramming the Immunosuppressive Metabolic Microenvironment

Chunjie Wang et al.

Summary: The pH-responsive nanomedicine prepared in this study has shown promising results in enhancing the therapeutic efficacy of radiotherapy against tumors by neutralizing tumor acidity and inhibiting IDO1, resulting in robust antitumor immunity and suppression of tumor metastasis and recurrence.

ADVANCED MATERIALS (2022)

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Review Immunology

Germinal Centers

Gabriel D. Victora et al.

Summary: This paper reviews recent developments in the field of germinal center (GC) biology, specifically in GCs induced by infection or immunization. It summarizes the phenotype and function of different cell types in the GC, focusing on GC B cells. It also examines the cellular and molecular basis of affinity-dependent selection within the GC and the export of memory and plasma cells. Additionally, it provides an overview of the emerging field of GC clonal dynamics and its impact on the diversity of antibodies secreted into serum.

ANNUAL REVIEW OF IMMUNOLOGY (2022)

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Review Pathology

Extrachromosomal DNA: An Emerging Hallmark in Human Cancer

Sihan Wu et al.

Summary: This review discusses the formation and function of circular, extrachromosomal pieces of DNA (ecDNA) found in cancer, as well as their contribution to tumor pathogenesis, drug resistance, and accelerated cancer evolution.

ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE (2022)

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Article Oncology

Lactic acid promotes PD-1 expression in regulatory T cells in highly glycolytic tumor microenvironments

Shogo Kumagai et al.

Summary: In highly glycolytic tumors, regulatory T (Treg) cells have higher PD-1 expression compared to effector T cells. Under low-glucose conditions, Treg cells actively absorb lactic acid through monocarboxylate transporter 1 (MCT1), promoting the expression of PD-1, while PD-1 expression by effector T cells is dampened. PD-1 blockade invigorates PD-1-expressing Treg cells, resulting in treatment failure.

CANCER CELL (2022)

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Editorial Material Oncology

Dangerous dynamic duo: Lactic acid and PD-1 blockade

Sheila Johnson et al.

Summary: The study reveals lactic acid as a mediator of checkpoint blockade resistance. It shows that tumor-derived lactic acid promotes T regulatory cell (Treg) activity and impairs CD8(+) T cell function. Additionally, the study demonstrates that PD-1 blockade synergizes with lactic acid to enhance Treg suppression and impede antitumor immunity.

CANCER CELL (2022)

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Article Biochemistry & Molecular Biology

Magnesium sensing via LFA-1 regulates CD8+ T cell effector function

Jonas Loetscher et al.

Summary: This study reveals the importance of extracellular magnesium in cellular immunity, particularly in the activation of the co-stimulatory molecule LFA-1. The findings demonstrate that magnesium-sufficiency enhances the function of immune cells and the effectiveness of T cell therapies. Low serum magnesium levels are associated with disease progression and reduced overall survival in patients receiving CAR T cell and immune checkpoint antibody treatments.

CELL (2022)

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Review Biochemistry & Molecular Biology

In Vivo Anticancer Activity of AZD3965: A Systematic Review

Ana Silva et al.

Summary: The transportation of lactate produced by glycolytic cancer cells plays a crucial role in cancer development, with MCT1 being a key transporter. The specific MCT1 inhibitor AZD3965 has shown promising anticancer effects in vivo, especially in combination therapy. This suggests its potential as a valuable treatment option in clinical settings.

MOLECULES (2022)

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Article Genetics & Heredity

The genomic and spatial mobility of extrachromosomal DNA and its implications for cancer therapy

Eric van Leen et al.

Summary: This Perspective explores the spatial and genomic mobility of extrachromosomal DNA within the cell and proposes how these properties may be harnessed for therapeutic benefit.

NATURE GENETICS (2022)

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Review Gastroenterology & Hepatology

Neutrophils as potential therapeutic targets in hepatocellular carcinoma

Daniel Geh et al.

Summary: The success of atezolizumab plus bevacizumab treatment has led to a shift towards combination therapies in the treatment of hepatocellular carcinoma (HCC) that include cancer immunotherapies. The focus of cancer immunotherapy has primarily been on immune checkpoints, but emerging evidence supports the role of neutrophils as important contributors to the development and progression of HCC. Neutrophil-targeted therapies are now being explored in clinical trials and may have therapeutic benefits, including enhancing the effectiveness of conventional immunotherapy.

NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY (2022)

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Article Multidisciplinary Sciences

Age influences on the molecular presentation of tumours

Constance H. Li et al.

Summary: This article investigates the association between aging and molecular alterations in cancer development, and identifies prognostic biomarkers through analysis of multiple cancer datasets. The results show that age influences the number and timing of mutations in tumors, and is associated with specific mutation patterns. Known cancer driver genes are also found to be age-dependent, and these mutations have an impact on the tumor transcriptome and clinical outcomes, particularly in brain cancers.

NATURE COMMUNICATIONS (2022)

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Review Oncology

Hallmarks of Cancer: New Dimensions

Douglas Hanahan

Summary: The concept of the hallmarks of cancer is a tool for simplifying the complexity of cancer phenotypes and genotypes into basic principles. This article proposes phenotypic plasticity and disrupted differentiation as distinct hallmark capabilities, and discusses nonmutational epigenetic reprogramming and polymorphic microbiomes as enabling characteristics. Additionally, the importance of senescent cells in the tumor microenvironment is highlighted. The integrative concept of the hallmarks of cancer helps in understanding the mechanisms of cancer development and applying that knowledge to cancer medicine.

CANCER DISCOVERY (2022)

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Article Immunology

Altered Frequencies and Functions of Innate Lymphoid Cells in Melanoma Patients Are Modulated by Immune Checkpoints Inhibitors

Costanza Maria Cristiani et al.

Summary: Monoclonal antibodies targeting immune checkpoints have shown improved clinical outcomes for patients with malignant melanoma, but the underlying mechanisms are not fully understood. This study investigated the effects of immune checkpoint inhibitors on innate lymphoid cells (ILCs) and the impact of melanoma cells on ILC functions. The findings suggest that PD-1 blockade can affect the proportions and functions of ILCs in melanoma patients, and specific subpopulations are associated with treatment response.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Medicine, General & Internal

Expression of the Immune Checkpoint Protein VISTA Is Differentially Regulated by the TGF-β1-Smad3 Signaling Pathway in Rapidly Proliferating Human Cells and T Lymphocytes

Stephanie Schlichtner et al.

Summary: Immune checkpoint protein VISTA plays a crucial role in anti-cancer immune evasion pathways and is regulated by the TGF-beta-Smad3 signaling pathway, but this regulation varies in T cells.

FRONTIERS IN MEDICINE (2022)

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Review Genetics & Heredity

Extrachromosomal DNA in Cancer

Vineet Bafna et al.

Summary: In cancer, the amplification of oncogenes on circular extrachromosomal DNA (ecDNA) elements drives tumor formation and progression. ecDNA increases oncogene copy number, promotes genetic heterogeneity, and results in treatment resistance. It also alters the transcriptional landscape of tumors. Current tools are limited in resolving the complex changes in DNA structure and dynamics caused by ecDNA, but new tools are emerging.

ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS (2022)

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Review Immunology

Development of neoantigens: from identification in cancer cells to application in cancer vaccines

Nasim Ebrahimi et al.

Summary: The discovery and utilization of neoantigens in cancer vaccines show promising results in cancer immunotherapy as they specifically target tumor cells without harming healthy cells. Advances in genome sequencing and bioinformatics have made it possible to detect, identify, and design effective neoantigens for personalized cancer vaccines. Clinical trials on neoantigen-based vaccines are ongoing to assess their advantages and limitations in cancer treatment.

EXPERT REVIEW OF VACCINES (2022)

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Article Oncology

Fatty acid-binding protein 5 limits the generation of Foxp3+ regulatory T cells through regulating plasmacytoid dendritic cell function in the tumor microenvironment

Shuhei Kobayashi et al.

Summary: This study shows that FABP5 in pDCs regulates tumor immunity by controlling lipid metabolism, affecting inflammatory gene expression and supporting T cell generation.

INTERNATIONAL JOURNAL OF CANCER (2022)

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Article Immunology

Tertiary lymphoid structures generate and propagate anti-tumor antibody-producing cells in renal cell cancer

Maxime Meylan et al.

Summary: The presence of intratumoral tertiary lymphoid structures (TLS) is associated with positive clinical outcomes and responses to immunotherapy in renal cell carcinoma (RCC). B cells are enriched in TLS and demonstrate diverse maturation stages, with the presence of fully mature clonotypes. Additionally, IgG-and IgA-producing plasma cells (PCs) disseminate into the tumor beds along fibroblastic tracks in TLS+ tumors, indicating potential anti-tumor effector activity. Furthermore, the presence of IgG-stained tumor cells correlates with therapeutic responses and progression-free survival in RCC patients treated with immune checkpoint inhibitors.

IMMUNITY (2022)

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Review Immunology

CD36, a signaling receptor and fatty acid transporter that regulates immune cell metabolism and fate

Yiliang Chen et al.

Summary: CD36 functions as both a signaling receptor and fatty acid transporter in various immune and non-immune cells. This review summarizes how its dual functions determine immune cell functions and fates, which contribute to common diseases including atherosclerosis and tumor progression.

JOURNAL OF EXPERIMENTAL MEDICINE (2022)

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Review Oncology

Gut microbiota influence immunotherapy responses: mechanisms and therapeutic strategies

Yuting Lu et al.

Summary: The gut microbiota play a crucial role in modulating antitumor immunity and enhancing the efficacy of cancer immunotherapies, particularly immune checkpoint inhibitors. Metabolites are a key mechanism through which the gut microbiota impact antitumor immune responses.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Oncology

Hypoxia-inducible factors: master regulators of hypoxic tumor immune escape

Qinghua Wu et al.

Summary: Hypoxia in the tumor microenvironment weakens cytotoxic T cell function and promotes recruitment of regulatory T cells, thereby reducing tumor immunogenicity. Hypoxia-inducible factors (HIFs), especially HIF1A and HIF2A, play important roles in tumor immune escape through various mechanisms. Understanding these mechanisms can lead to the development of targeted therapies for tumor treatment.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Immunology

Innate lymphoid cells and cancer

Nicolas Jacquelot et al.

Summary: Innate lymphoid cells (ILCs) play a role in immune responses and have been found to have pleiotropic effects in various tissues, including both tissue repair and immunopathology toward allergens and promotion of tumorigenesis. Recent studies suggest that non-NK ILCs might be harnessed for anti-tumor responses. Gabrielle Belz and colleagues review the influence of ILCs on cancer immune responses.

NATURE IMMUNOLOGY (2022)

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Article Immunology

PERK is a critical metabolic hub for immunosuppressive function in macrophages

Lydia N. Raines et al.

Summary: This study reveals the importance of PERK signaling and PSAT1-mediated serine metabolism in promoting the immunosuppressive function of M2 macrophages, providing new insights into the molecular mechanisms of immune cell suppressive phenotype.

NATURE IMMUNOLOGY (2022)

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Review Oncology

B cells and tertiary lymphoid structures as determinants of tumour immune contexture and clinical outcome

Wolf H. Fridman et al.

Summary: B cells play a critical role in the tumor microenvironment, particularly within tertiary lymphoid structures (TLS). The presence of mature TLS, high density of B cells and plasma cells, and antibodies targeting tumor-associated antigens are associated with favorable clinical outcomes and response to immunotherapy. However, polyclonal B cell activation can lead to pro-inflammatory responses. Novel therapeutic approaches are being explored to enhance the development of TLS and anti-tumor B cells for cancer therapy.

NATURE REVIEWS CLINICAL ONCOLOGY (2022)

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Review Oncology

Neutrophil extracellular traps in cancer

Leonardo Cristinziano et al.

Summary: Neutrophils, in addition to their well-known functions in the acute phases of the immune response, play important roles in tumor initiation and progression through the release of various mediators. Neutrophil extracellular traps (NETs), composed of DNA and decorating proteins, not only trap and kill extracellular pathogens, but also have both pro-inflammatory and anti-inflammatory effects in cancer-related inflammation. This review focuses on the mechanisms underlying the emerging effects of NETs in cancer initiation and progression.

SEMINARS IN CANCER BIOLOGY (2022)

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Review Immunology

Agents of cancer immunosurveillance: HSPs and dsDNA

Devanshi A. Nayak et al.

Summary: Tumor immunosurveillance relies on interactions between tumor cell-derived molecules and corresponding receptors on antigen presenting cells (APCs) to eliminate tumor cells. The adjuvanticity of tumor-derived HSPs and dsDNA is necessary for tumor-specific immunity. Understanding the immune system's interactions with precancerous neoplastic cells is crucial for improved cancer prevention measures.

TRENDS IN IMMUNOLOGY (2022)

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Editorial Material Immunology

Magnesium for T cells: strong to the finish

Santosha Vardhana et al.

Summary: This article discusses the role of spinach in enhancing strength and defending against bullies, and the importance of dietary magnesium ion deficiency affecting the activity of the key molecule LFA-1, which hinders the ability of CD8(+) T cells to combat various bullies.

TRENDS IN IMMUNOLOGY (2022)

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Article Multidisciplinary Sciences

A non-dividing cell population with high pyruvate dehydrogenase kinase activity regulates metabolic heterogeneity and tumorigenesis in the intestine

Carlos Sebastian et al.

Summary: This study reveals that the histone deacetylase SIRT6 controls tumor initiation in intestinal cancer through regulating glucose metabolism. The loss of SIRT6 leads to an increase in the number of intestinal stem cells (ISCs), resulting in enhanced tumor initiating potential. The researchers found a metabolic compartmentalization within the intestinal epithelium and adenomas, where a rare population of cells exhibit features of Warburg-like metabolism characterized by high pyruvate dehydrogenase kinase (PDK) activity. These cells are quiescent cells expressing +4 ISCs and enteroendocrine markers, and their active glycolysis suppresses ROS accumulation and enhances their stem cell and tumorigenic potential.

NATURE COMMUNICATIONS (2022)

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Article Immunology

B Cells Are Required to Generate Optimal Anti-Melanoma Immunity in Response to Checkpoint Blockade

Shubhra Singh et al.

Summary: In this study, the role of B cells in anti-melanoma immunity was investigated. The researchers found that B cells were required for the effectiveness of PD-L1 antibody monotherapy and combination therapy with PD-L1 antibody and TLR-7/8 agonist. However, B cells were not essential for anti-CTLA-4 antibody activity. The presence of B cell chemokine CXCL13 and B cells together with CD8(+) T cells in tumors were strongly associated with improved overall survival in melanoma patients.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

Intratumoral immunotherapy relies on B and T cell collaboration

Idit Sagiv-Barfi et al.

Summary: Antitumor T cell responses play a crucial role in cancer immunotherapy, but other immune system components are also necessary for effective T cell responses. This study demonstrates that combining Toll-like receptor 9 agonist CpG and Fc-fused IL-12 protein can induce body-wide therapeutic responses in multiple cancer models. These responses depend not only on T cells but also on B cells, which are activated by the treatment and required for optimal T cell activation. The addition of an agonistic antibody against OX40 further enhances T cell activation and therapeutic responses. These findings suggest the potential success of the combination of CpG, anti-OX40, and IL-12Fc in cancer patients and highlight the importance of B and T cell collaboration in this combination immunotherapy.

SCIENCE IMMUNOLOGY (2022)

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Review Immunology

Human dendritic cells in cancer

Egle Kvedaraite et al.

Summary: In this review, the authors discuss the antitumor and tolerogenic responses of dendritic cells (DCs) in cancer, as well as the contributions of different subsets and the recently described mature DCs enriched in immunoregulatory molecules across human tumors.

SCIENCE IMMUNOLOGY (2022)

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Review Hematology

Local and systemic features of ILC immunometabolism

Laura Surace et al.

Summary: This review discusses the role of innate lymphoid cells (ILCs) as metabolic sentinels and how specific activities of ILC subsets influence homeostasis and disease. Recent studies have found that ILCs' metabolism, phenotype, and function are shaped by signals from the tissue microenvironment. ILCs have emerged as crucial sensors of metabolic stress.

CURRENT OPINION IN HEMATOLOGY (2022)

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Review Oncology

Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

Liangliang Xu et al.

Summary: The development of combination immunotherapy based on regulatory mechanisms of the tumor immune microenvironment (TIME) is promising. This review focuses on recent advances in single-cell transcriptomics and spatial transcriptomics for the study of the systemic tumor immune environment (STIE), TIME, and their interactions. The understanding of heterogeneity and dynamic changes in response to immunotherapy may enhance treatment efficacy.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Cell Biology

Untangling the web of intratumour heterogeneity

Zheqi Li et al.

Summary: This article discusses the causes of intratumour heterogeneity (ITH) and its impact on immune escape and tumour progression. Although advances in technology and computational methods have allowed us to assess ITH more effectively, our understanding of the functional relevance of ITH remains limited.

NATURE CELL BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Fumarate suppresses B-cell activation and function through direct inactivation of LYN

Jie Cheng et al.

Summary: Activated B cells increase central carbon metabolism to meet their energy demands. The activation of B cells leads to reprogramming of the tricarboxylic acid cycle and increased expression of fumarate hydratase, resulting in decreased cellular fumarate levels. Fumarate accumulation inhibits B-cell activation, proliferation, and antibody production by directly inhibiting the activity of the tyrosine kinase LYN, a key component of the B-cell antigen receptor signaling pathway.

NATURE CHEMICAL BIOLOGY (2022)

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Review Immunology

The complex role of tumor-infiltrating macrophages

Anthos Christofides et al.

Summary: This article reviews the characteristics of tumor-associated macrophages (TAMs) and discusses the mechanisms that contribute to their pathological adaptations to the tumor microenvironment. TAMs play a crucial role in the tumor microenvironment and are closely associated with cancer progression.

NATURE IMMUNOLOGY (2022)

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Review Genetics & Heredity

Extrachromosomal DNA amplifications in cancer

Eunhee Yi et al.

Summary: This review discusses the latest understanding of extrachromosomal DNA (ecDNA) in cancers, including its properties and role in oncogenesis. The amplification of ecDNA is common in cancer and associated with worse patient outcomes. Recent studies have revealed the complex structure and functions of ecDNA, including its ability to act as an enhancer for genes on other ecDNAs or chromosomes. This knowledge opens up new opportunities for therapeutic interventions in cancer.

NATURE REVIEWS GENETICS (2022)

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Review Biochemistry & Molecular Biology

Gene regulation on extrachromosomal DNA

King L. Hung et al.

Summary: Amplification of oncogene expression through extrachromosomal DNA is prevalent in human cancer and is associated with poor outcomes. The formation of ecDNA hubs enables profound changes in gene regulation and allows for potent and combinatorial gene activation. Technological advancements in studying ecDNA gene regulation and structure provide insights into the distinct rules that govern cancer genes beyond chromosomes.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2022)

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Article Immunology

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein

Silvia Gaggero et al.

Science Immunology (2022)

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Article Cell Biology

Tumor metabolite lactate promotes tumorigenesis by modulating MOESIN lactylation and enhancing TGF-? signaling in regulatory T cells

Jian Gu et al.

Summary: The lactate in tumor microenvironment plays a crucial role in regulating Treg cells. It can improve Treg cell stability and function, while its degradation reduces Treg cell induction. Lactate modulates Treg cell generation through lactylation of MOESIN, leading to enhanced interaction with TGF-β receptor I and downstream SMAD3 signaling. Combining lactate dehydrogenase inhibitor with anti-PD-1 treatment shows stronger antitumor effects. MOESIN lactylation levels in Treg cells are associated with the response to anti-PD-1 treatment in hepatocellular carcinoma patients.

CELL REPORTS (2022)

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Review Immunology

Innate lymphoid cells in early tumor development

Kathrin Warner et al.

Summary: Innate lymphoid cells (ILCs), the innate counterparts of T cells, play a crucial role in immune responses and have a profound impact on diseases like cancer. ILCs can influence early tumor development.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Glutamine deprivation impairs function of infiltrating CD8+ T cells in hepatocellular carcinoma by inducing mitochondrial damage and apoptosis

Wei Wang et al.

Summary: Glutamine deprivation impairs the function of infiltrating CD8(+) T cells in hepatocellular carcinoma through mitochondrial damage and apoptotic pathways.

WORLD JOURNAL OF GASTROINTESTINAL ONCOLOGY (2022)

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Article Immunology

An innate IL-25-ILC2-MDSC axis creates a cancer-permissive microenvironment for Apc mutation-driven intestinal tumorigenesis

Eric Jou et al.

Summary: Intestinal IL-25-activated ILC2s create a cancer-permissive microenvironment, associated with reduced survival and increased MDSCs in colorectal cancer patients. Ablation of IL-25 signaling reduces tumors and extends lifespan, while therapeutic antibody blockade enhances antitumor immunity.

SCIENCE IMMUNOLOGY (2022)

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Review Oncology

TGF-β signaling in the tumor metabolic microenvironment and targeted therapies

Xueke Shi et al.

Summary: TGF-beta signaling plays a paradoxical role in cancer progression, acting as a tumor suppressor in early stages but a tumor promoter in late stages. It regulates cancer metabolic reprogramming and acts as a metabolic driver in the tumor metabolic microenvironment. Understanding the role of TGF-beta signaling in the tumor metabolic microenvironment is crucial for designing new cancer treatment strategies.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Biochemistry & Molecular Biology

Feedback loop between fatty acid transport protein 2 and receptor interacting protein 3 pathways promotes polymorphonuclear neutrophil myeloid-derived suppressor cells-potentiated suppressive immunity in bladder cancer

Xiaojun Shi et al.

Summary: This study discovered a feedback loop between FATP2 and RIPK3 pathways in PMN-MDSCs, which significantly promoted the synthesis of PGE2 and impaired the CD8(+) T cell functions. Combination therapy with inhibition of FATP2 and activation of RIPK3 effectively inhibited tumor growth.

MOLECULAR BIOLOGY REPORTS (2022)

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Review Immunology

Food for thought - ILC metabolism in the context of helminth infections

Marcel Michla et al.

Summary: This article reviews the complex interplay between helminth infections and ILC2 biology, and discusses the host's metabolic adaptation to helminth infections and the metabolic pathways fueling ILC2 responses. Understanding the metabolic restraints imposed by helminth infections may offer new therapeutic avenues in the future.

MUCOSAL IMMUNOLOGY (2022)

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Review Cell Biology

Metabolic communication in the tumour-immune microenvironment

Kung-Chi Kao et al.

Summary: The metabolically hostile tumour microenvironment can hinder immune cells and impede the effectiveness of immunotherapy. Metabolic communication between cancer cells and immune cells may play a crucial role in determining immune responses. Nutrient-limiting strategies may enhance anti-tumour immune responses.

NATURE CELL BIOLOGY (2022)

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Article Biotechnology & Applied Microbiology

Spermidine Promotes Nb CAR-T Mediated Cytotoxicity to Lymphoma Cells Through Elevating Proliferation and Memory

Hongxia Wang et al.

Summary: Our study found that spermidine can enhance the cytotoxicity of Nb CAR-T cells to lymphoma cells by promoting memory and proliferation, providing a meaningful approach to strengthen the anti-tumor effect of CAR-T cells.

ONCOTARGETS AND THERAPY (2022)

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Article Cell Biology

NLRP6 is required for cancer-derived exosome-modified macrophage M2 polarization and promotes metastasis in small cell lung cancer

Xinrui Rao et al.

Summary: This study discovered that SCLC patients with high expression of the M2 TAM marker had poorer prognosis and higher chances of metastasis. In a mouse model, infiltrating macrophages were observed in the metastatic foci. It was found that SCLC-derived exosomes induce the M2 switch via the NLRP6/NF-kappa B pathway, promoting SCLC metastasis.

CELL DEATH & DISEASE (2022)

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Article Multidisciplinary Sciences

Lactate increases stemness of CD8+T cells to augment anti-tumor immunity

Qiang Feng et al.

Summary: Lactate increases stemness of CD8(+) T cells and enhances anti-tumor immunity. It inhibits histone deacetylase activity, leading to increased expression of Tcf7 gene, and affects the stemness of T cells.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Metabolic control of CD47 expression through LAT2-mediated amino acid uptake promotes tumor immune evasion

Zenan Wang et al.

Summary: The authors demonstrate that doxorubicin promotes IL-18 secretion by tumor associated macrophages, leading to the upregulation of CD47 in osteosarcoma cells. By inhibiting LAT2, CD47 expression can be downregulated, enhancing macrophage infiltration and phagocytosis of tumor cells. These findings highlight the critical role of mutual regulation between macrophages and tumor cells in tumor immune evasion.

NATURE COMMUNICATIONS (2022)

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Article Immunology

Enforcing GLUT3 expression in CD8+ T cells improves fitness and tumor control by promoting glucose uptake and energy storage

Elisabetta Cribioli et al.

Summary: This study found that enforced expression of the high-affinity glucose transporter GLUT3 can improve metabolic fitness of tumor-directed T cells. GLUT3-OT1 T cells showed better tumor control and significantly improved survival in a melanoma model, with some treated mice being cured and protected from re-challenge, indicating long-term T cell persistence and memory formation.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Loss of CD47 alters CD8+T cell activation in vitro and immunodynamics in mice

Pulak R. Nath et al.

Summary: CD47 regulates the activation, proliferation, and fitness of CD8+ T cells in a context-dependent manner, with short-term stimuli enhancing the effector phenotypes of Cd47-deficient CD8+ T cells and persistent TCR stimulation limiting their effector phenotypes.

ONCOIMMUNOLOGY (2022)

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Article Oncology

Tumorous expression of NAC1 restrains antitumor immunity through the LDHA-mediated immune evasion

Yijie Ren et al.

Summary: This study investigates the role of nucleus accumbens-associated protein-1 (NAC1) in the tumor microenvironment and its impact on anti-tumor immunity. The results demonstrate that NAC1 negatively affects immune evasion by regulating lactate dehydrogenase A (LDHA) expression and lactic acid production. Targeting NAC1 therapeutically may be a potential strategy to enhance cancer immunotherapy.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Review Oncology

Role of myeloid-derived suppressor cells in the formation of pre-metastatic niche

Guoqi Ya et al.

Summary: Metastasis is a complex process that relies on the interaction between tumor cells and host organs, with the formation of a pre-metastasis niche being crucial. Myeloid-derived suppressor cells play a key role in this process, and targeting these cells as a therapeutic strategy may help inhibit the formation of the pre-metastasis niche and curb tumor metastasis.

FRONTIERS IN ONCOLOGY (2022)

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Article Immunology

BATF epigenetically and transcriptionally controls the activation program of regulatory T cells in human tumors

Kota Itahashi et al.

Summary: Research has shown that Treg cells in the TME undergo a distinct open chromatin profile, with key transcription factors including BATF, IRF4, NF-κB, and NR4A, among which BATF serves as a crucial regulator influencing the differentiation and activation of Treg cells in the TME through epigenetic control of activation-associated gene expression. BATF deficiency may inhibit tumor growth, and high levels of BATF expression are associated with poor prognosis.

SCIENCE IMMUNOLOGY (2022)

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Article Surgery

Characterization of glucose metabolism in breast cancer to guide clinical therapy

Yingying Mei et al.

Summary: A novel glycometabolism-related gene (GRG) signature was constructed to predict overall survival (OS), immune infiltration, and therapeutic response in breast cancer patients. High-risk patients correlated with poorer OS, higher M2 macrophage infiltration, and greater sensitivity to Lapatinib. SDC1 was identified as a candidate target and patients in the low-SDC1 group had a better OS.

FRONTIERS IN SURGERY (2022)

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Review Oncology

The role of VISTA in the tumor microenvironment

Dina Rabadi et al.

Summary: VISTA is a negative immune checkpoint that is expressed on multiple immune cell subsets. It plays a significant role in maintaining T cell stability and regulating tumor cell activities. Blocking VISTA can enhance anti-tumor immune response, and combining it with other immune checkpoint inhibitors can further improve therapeutic efficacy.

JOURNAL OF CANCER METASTASIS AND TREATMENT (2022)

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Article Cell Biology

Balance between immunoregulatory B cells and plasma cells drives pancreatic tumor immunity

Bhalchandra Mirlekar et al.

Summary: The dysregulation of B cells in patients and tumor-bearing mice often leads to the failure of anti-tumor immune responses. By targeting the signaling network in B cells, the differentiation of B cells into anti-tumor plasma cells can be restored, resulting in increased accumulation of effector T cells and plasma cells in tumors and making pancreatic tumors sensitive to immunotherapy.

CELL REPORTS MEDICINE (2022)

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Article Immunology

Serine metabolism orchestrates macrophage polarization by regulating the IGF1-p38 axis

Xiao Shan et al.

Summary: This study reveals that suppressing serine metabolism enhances the polarity of interferon-gamma-activated macrophages but suppresses the polarity of interleukin-4-activated macrophages. Serine metabolism deficiency leads to increased IGF1 expression, which in turn activates the p38-dependent JAK-STAT1 axis to regulate macrophage polarization.

CELLULAR & MOLECULAR IMMUNOLOGY (2022)

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Article Oncology

Interrogation of T Cell-enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism

R. Alex Harbison et al.

Summary: The metabolic features of the tumor microenvironment can impede anti-tumor immunity. This study focuses on the metabolic gene expression in T cell-infiltrated human papillomavirus-related head and neck squamous cell carcinomas. The overexpression of polyamine metabolism genes is associated with T cell infiltration, cancer recurrence, overall survival, and molecular subtype.

CANCER RESEARCH COMMUNICATIONS (2022)

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Review Oncology

Polyamines in cancer: integrating organismal metabolism and antitumour immunity

Cassandra E. Holbert et al.

Summary: Polyamines play a crucial role in the initiation and progression of cancer, and dysregulation of their metabolism is common in many cancers. Recent research suggests that polyamines can affect the antitumour immune response and contribute to the lack of response to immune checkpoint blockade in immunologically 'cold' tumours. Furthermore, the interaction between the microbiota and tissues can significantly alter polyamine metabolism, content, and function.

NATURE REVIEWS CANCER (2022)

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Review Oncology

Tumour-infiltrating B cells: immunological mechanisms, clinical impact and therapeutic opportunities

Celine M. Laumont et al.

Summary: Tumour-infiltrating B cells and plasma cells have a crucial role in tumour control, promoting antitumour immunity through unique antigen presentation, assembling and perpetuating immunologically 'hot' tumour microenvironments, combating immune editing and tumour heterogeneity.

NATURE REVIEWS CANCER (2022)

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Article Endocrinology & Metabolism

Switching to the cyclic pentose phosphate pathway powers the oxidative burst in activated neutrophils

Emily C. Britt et al.

Summary: Neutrophils undergo metabolic reconfigurations towards pentose cycling upon activation, which maximizes NADPH yield to fuel superoxide production. Disruptions of pentose cycle greatly suppress neutrophil effector functions.

NATURE METABOLISM (2022)

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Review Immunology

Tumor-associated myeloid cells: diversity and therapeutic targeting

Alberto Mantovani et al.

Summary: Myeloid cells in tumor tissues, including tumor-associated macrophages and tumor-associated neutrophils, play crucial roles in tumor growth and invasion. In recent years, successful therapeutic approaches have been developed and tested in preclinical cancer models, with some strategies reaching clinical trials.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Editorial Material Oncology

Improving immunotherapy response through the use of designer bacteria

Matthew E. Griffin et al.

Summary: Reprogramming tumor microenvironment via engineered bacteria can enhance the efficacy of anti-PD-L1 immunotherapy, as shown in a recent study published in Nature by Canale et al.

CANCER CELL (2021)

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Review Immunology

Tumor-infiltrating dendritic cell states are conserved across solid human cancers

Genevieve M. Gerhard et al.

Summary: This article discusses the expanding view of dendritic cell heterogeneity in human tumors, as revealed through meta-analysis of single-cell transcriptome profiling studies. It further examines the conserved tumor-infiltrating DC states across patients, cancer types, and species, and considers the fundamental and clinical relevance of these findings. Finally, an outlook on research opportunities to explore mechanisms governing tumor-infiltrating DC behavior and functions is provided.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Immunology

B cells and cancer: To B or not to B?

Wolf Herman Fridman et al.

Summary: Recent studies have suggested that B cells in the tumor microenvironment may play a significant role in presenting tumor-associated antigens to T cells and producing antibodies that enhance antigen presentation, ultimately impacting cancer clinical outcomes. Immune complexes formed by B cells can also have deleterious effects through inflammation, angiogenesis, and immunosuppression via macrophage and complement activation.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Immunology

Mitochondrial stress induced by continuous stimulation under hypoxia rapidly drives T cell exhaustion

Nicole E. Scharping et al.

Summary: Continuous TCR signaling and hypoxia increase Blimp-1, suppressing mitochondrial reprogramming and generating reactive oxygen species, leading to T cell exhaustion. Mitigating T cell-intrinsic ROS and reducing tumor hypoxia can limit T cell exhaustion, synergizing with immunotherapy.

NATURE IMMUNOLOGY (2021)

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Editorial Material Immunology

Mitochondria orchestrate T cell fate and function

Xia Liu et al.

Summary: Investigation of molecular processes related to mitochondrial reprogramming and metabolic stress in antigen-experienced T cells within tumor microenvironments reveals mechanisms underlying T cell exhaustion and dysfunction, aiding in the development of novel strategies for tumor immunotherapy.

NATURE IMMUNOLOGY (2021)

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Article Immunology

Group 2 innate lymphoid cells promote TNBC lung metastasis via the IL-13-MDSC axis in a murine tumor model

Na Zhao et al.

Summary: ILC2s play a key role in TNBC lung metastasis, potentially through the ILC2-derived IL-13-activated MDSC pathway.

INTERNATIONAL IMMUNOPHARMACOLOGY (2021)

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Review Immunology

VISTA: A Mediator of Quiescence and a Promising Target in Cancer Immunotherapy

Long Yuan et al.

Summary: VISTA, a B7 family member, plays a role in maintaining immune cell quiescence and is a potential target for cancer immunotherapy. It reprograms macrophages and its interaction with ligands is regulated by pH, suggesting targeting intratumoral pH could enhance antitumor immune responses. Additionally, differences among VISTA therapeutics and their potential as candidate immunotherapies are being actively researched.

TRENDS IN IMMUNOLOGY (2021)

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Article Oncology

Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries

Hyuna Sung et al.

Summary: The global cancer burden in 2020 saw an estimated 19.3 million new cancer cases and almost 10.0 million cancer deaths. Female breast cancer surpassed lung cancer as the most commonly diagnosed cancer, while lung cancer remained the leading cause of cancer death. These trends are expected to rise in 2040, with transitioning countries experiencing a larger increase compared to transitioned countries due to demographic changes and risk factors associated with globalization and a growing economy. Efforts to improve cancer prevention measures and provision of cancer care in transitioning countries will be crucial for global cancer control.

CA-A CANCER JOURNAL FOR CLINICIANS (2021)

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Editorial Material Cell Biology

Mitochondrial dysfunction defines T cell exhaustion

Gonzalo Soto-Heredero et al.

Summary: The research indicates that continuous antigen stimulation and severe hypoxic conditions can lead to T cell exhaustion, thereby losing their anticancer effects.

CELL METABOLISM (2021)

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Article Cell Biology

CD36-mediated ferroptosis dampens intratumoral CD8+ T cell effector function and impairs their antitumor ability

Xingzhe Ma et al.

Summary: Understanding the mechanisms of how T cells become dysfunctional in a tumor microenvironment is crucial for cancer immunotherapy. This study found that CD36 expression in tumor-infiltrating CD8(+) T cells, induced by TME cholesterol, is associated with tumor progression and poor survival, and that genetic ablation of Cd36 in these T cells leads to enhanced tumor eradication. Targeting CD36 or inhibiting ferroptosis could restore T cell function and enhance antitumor efficacy, especially in combination with anti-PD-1 antibodies.

CELL METABOLISM (2021)

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Article Multidisciplinary Sciences

Metabolic modulation of tumours with engineered bacteria for immunotherapy

Fernando P. Canale et al.

Summary: Engineered bacteria were developed to convert ammonia to l-arginine in tumors, increasing intratumoral l-arginine concentrations, T cell infiltration, and synergistic effects with PD-L1 blocking antibodies in tumor clearance. These results indicate that microbial therapies can enhance immunotherapy efficacy by modulating the tumor microenvironment.

NATURE (2021)

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Article Multidisciplinary Sciences

ecDNA hubs drive cooperative intermolecular oncogene expression

King L. Hung et al.

Summary: Extrachromosomal DNA (ecDNA) hubs are clusters of ecDNAs within the nucleus that enable intermolecular enhancer-gene interactions, promoting oncogene overexpression. The protein-tethered ecDNA hubs facilitate intermolecular transcriptional regulation, serving as units of oncogene function and potential targets for cancer therapy.

NATURE (2021)

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Article Immunology

Dichotomous metabolic networks govern human ILC2 proliferation and function

Laura Surace et al.

Summary: ILC2 metabolism in humans is not well studied, but research shows that ILC2 relies on different metabolic pathways to sustain proliferation and function, with glycolysis and amino acids playing important roles post-activation for IL-13 production.

NATURE IMMUNOLOGY (2021)

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Article Immunology

Tumor-induced reshuffling of lipid composition on the endoplasmic reticulum membrane sustains macrophage survival and pro-tumorigenic activity

Giusy Di Conza et al.

Summary: The study reveals how tumor-derived lipids activate IRE1-XBP1 and IRE1-STAT3 endoplasmic reticulum stress response pathways to orchestrate pro-tumorigenic features and survival in tumor-associated macrophages.

NATURE IMMUNOLOGY (2021)

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Article Immunology

Analysis of classical neutrophils and polymorphonuclear myeloid-derived suppressor cells in cancer patients and tumor-bearing mice

Filippo Veglia et al.

Summary: In this study, the heterogeneity of polymorphonuclear neutrophils (PMNs) in cancer was characterized using various methods, revealing different populations of PMNs. Evidence was provided to show that PMN-MDSCs are a distinct population of PMNs with unique features and potential for selective targeting opportunities.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Multidisciplinary Sciences

Metabolic support of tumour-infiltrating regulatory T cells by lactic acid

McLane J. Watson et al.

Summary: T-reg cells exhibit broad heterogeneity in glucose metabolism within normal and transformed tissues, utilizing an alternative metabolic pathway to maintain their suppressive function and proliferation. Glucose uptake is correlated with poorer suppressive function and long-term instability, while high-glucose conditions impair T-reg cell function and stability. Additionally, T-reg cells upregulate pathways involved in the metabolism of lactic acid, with lactate uptake being dispensable for peripheral T-reg cells but required intratumorally for slowed tumor growth and increased response to immunotherapy.

NATURE (2021)

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Article Multidisciplinary Sciences

Tumor methionine metabolism drives T-cell exhaustion in hepatocellular carcinoma

Man Hsin Hung et al.

Summary: The study reveals a correlation between T-cell exhaustion and overall survival in hepatocellular carcinoma patients, suggesting a link to oncogenic reprogramming of methionine metabolism. Reprogramming tumor methionine metabolism could be a potential therapeutic strategy to enhance HCC immunity.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Plasma cells are enriched in localized prostate cancer in Black men and are associated with improved outcomes

Adam B. Weiner et al.

Summary: Studies suggest that prostate tumors from Black men or men of African ancestry exhibit increased plasma cell infiltrate, augmented NK cell activity, and IgG expression, which correlates with improved recurrence-free survival post-surgery. These findings nominate plasma cells as drivers of prostate cancer immune-responsiveness and may explain why Black men show greater benefits from immune-based treatment.

NATURE COMMUNICATIONS (2021)

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Article Medicine, General & Internal

Enhanced antitumor efficacy of a novel oncolytic vaccinia virus encoding a fully monoclonal antibody against T-cell immunoglobulin and ITIM domain (TIGIT)

Shuguang Zuo et al.

Summary: The study demonstrates that VV-alpha-TIGIT exhibits effective anti-tumor efficacy in various tumor models, particularly achieving approximately 70% complete tumor regression in an ascites tumor model. Treatment with VV-alpha-TIGIT also significantly increases the recruitment and activation of T cells in TME.

EBIOMEDICINE (2021)

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Article Multidisciplinary Sciences

Lactate supports a metabolic-epigenetic link in macrophage polarization

Jordan T. Noe et al.

Summary: Lactate accumulation plays a key role in the activation of M2 macrophages, promoting histone acetylation, M2 gene transcription, and functional immune suppression. Metabolism of M2 macrophages is dependent on mitochondrial function and the glucose/lactate metabolic pathway.

SCIENCE ADVANCES (2021)

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Review Immunology

Innate Lymphoid Cells and Adaptive Immune Cells Cross-Talk: A Secret Talk Revealed in Immune Homeostasis and Different Inflammatory Conditions

Vijay Kumar

Summary: The inflammatory immune response has evolved to protect the host from different pathogens, allergens, and endogenous death or damage-associated molecular patterns. Failure of the inflammatory immune response to subside to its normal level generates chronic inflammatory conditions, including autoimmune diseases and cancer. Innate lymphoid cells (ILCs) play a crucial role in generating the pro-inflammatory immune response, while adaptive immune cells, including different types of T and B cells, are major players in the pathogenesis of autoimmune diseases and cancers.

INTERNATIONAL REVIEWS OF IMMUNOLOGY (2021)

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Article Immunology

Cutting Edge: mTORC1 Inhibition in Metastatic Breast Cancer Patients Negatively Affects Peripheral NK Cell Maturation and Number

Laurie Besson et al.

Summary: The mTOR inhibitor everolimus treatment in metastatic breast cancer patients was found to inhibit mTORC1 activity in peripheral NK cells while mTORC2 activity was preserved. This led to a contraction of the NK cell pool and an overall decrease in their maturation, although the phenotype and function of the remaining NK cell population were less affected. This study represents the first in vivo characterization of the role of mTOR in human NK cells.

JOURNAL OF IMMUNOLOGY (2021)

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Article Multidisciplinary Sciences

Cell-programmed nutrient partitioning in the tumour microenvironment

Bradley Reinfeld et al.

Summary: The study found that in the tumor microenvironment, different cell types have varying abilities to access and consume glucose and glutamine, with nutrient partitioning being programmed in a cell-intrinsic manner through mTORC1 signaling and the expression of genes related to glucose and glutamine metabolism.

NATURE (2021)

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Article Multidisciplinary Sciences

Atlas of breast cancer infiltrated B-lymphocytes revealed by paired single-cell RNA-sequencing and antigen receptor profiling

Qingtao Hu et al.

Summary: Characterization of tumor-infiltrated B cells in breast tumors through single-cell RNA sequencing and antigen receptor analysis reveals significant heterogeneity and features of infiltrated B cells. Results suggest local differentiation of infiltrated B cells within breast tumors. B cell signatures based on single-cell RNA sequencing results are associated with survival in breast tumor patients.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

PPAR? drives IL-33-dependent ILC2 pro-tumoral functions

Giuseppe Ercolano et al.

Summary: The expression of PPARγ in ILC2s sustains type-2 cytokines secretion and supports their pro-tumorigenic role in preclinical cancer models. Pharmacologic inhibition or genetic deletion of PPARγ in ILC2s significantly impair IL-33-induced Type-2 cytokine production and mitochondrial fitness.

NATURE COMMUNICATIONS (2021)

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Review Oncology

Metabolic Rewiring in Radiation Oncology Toward Improving the Therapeutic Ratio

Marike W. van Gisbergen et al.

Summary: Malignant cells tend to rewire their metabolic pathways to meet the anabolic demands of proliferation, and differences in metabolic patterns between normal tissue and malignant cells can be utilized to improve the therapeutic ratio. Modulation of cellular metabolism is an emerging field proposing various strategies to optimize treatment outcomes for primary tumors and metastatic lesions.

FRONTIERS IN ONCOLOGY (2021)

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Article Oncology

Metastasis-Entrained Eosinophils Enhance Lymphocyte-Mediated Antitumor Immunity

Sharon Grisaru-Tal et al.

Summary: Research has found that eosinophils exhibit antitumor activities in the metastatic tumor microenvironment, and can be trained by the TME to adopt antitumorigenic properties, potentially leading to the development of eosinophil-targeted therapeutics.

CANCER RESEARCH (2021)

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Editorial Material Biochemistry & Molecular Biology

Polyamine: A metabolic compass for T helper cell fate direction

Hao Shi et al.

Summary: The interplay between metabolic and epigenetic remodeling is crucial for cell fate control, as shown in this study by Puleston et al. and Wagner et al. Using metabolomic, computational, and genetic approaches, they reveal that polyamine metabolism directs T helper cell lineage choices, epigenetic state, and pathogenic potential in inflammation.

CELL (2021)

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Article Biochemistry & Molecular Biology

Metabolic modeling of single Th17 cells reveals regulators of autoimmunity

Allon Wagner et al.

Summary: The study utilized the Compass algorithm in combination with single-cell RNA sequencing and flux balance analysis to reveal the link between metabolic states and functional variability of Th17 cells, validating the importance of metabolic switch for Th17 pathogenicity.

CELL (2021)

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Article Biochemistry & Molecular Biology

Dysregulation of ILC3s unleashes progression and immunotherapy resistance in colon cancer

Jeremy Goc et al.

Summary: Research shows that ILC3s play a protective role in cancer, and alterations in CRC may lead to dysfunctional adaptive immunity, tumor progression, and immunotherapy resistance.

CELL (2021)

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Article Biochemistry & Molecular Biology

Polyamine metabolism is a central determinant of helper T cell lineage fidelity

Daniel J. Puleston et al.

Summary: Polyamine synthesis plays a critical role in T cell activation and differentiation, regulating CD4(+) T cells' function and epigenetic remodeling. Studies have revealed the significance of polyamine metabolism in controlling the fate of T-H cell subsets, with deficiency leading to aberrant expression of cytokines and transcription factors.

CELL (2021)

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Article Cell Biology

Regulation of humoral immune response by HIF-1α-dependent metabolic reprogramming of the germinal center reaction

Lingyun Li et al.

Summary: The study reveals the crucial role of HIF-1 alpha in regulating humoral immunity through metabolic reprogramming in GC B-cells, with deficiency impairing the functional GC response and affecting the generation of high-affinity plasma cells. This newly discovered metabolic characteristic of GC B-cells will enhance understanding of GC biology and B-cell lymphomagenesis.

CELLULAR IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

The Role of Tumor Associated Macrophages (TAMs) in Cancer Pro-gression, Chemoresistance, Angiogenesis and Metastasis-Current Status

Siva Dallavalasa et al.

Summary: TAMs in the tumor microenvironment play a significant role in promoting cancer cell metastasis and influencing angiogenesis, as well as inducing multidrug resistance.

CURRENT MEDICINAL CHEMISTRY (2021)

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Article Immunology

Uptake of oxidized lipids by the scavenger receptor CD36 promotes lipid peroxidation and dysfunction in CD8+ T cells in tumors

Shihao Xu et al.

Summary: The accumulation of lipids in the tumor microenvironment is associated with dysfunction of CD8(+) T cells, mediated in part by the CD36 receptor and its promotion of lipid uptake and peroxidation. Inhibiting p38 kinase or resolving lipid peroxidation may restore effector T cell functions and provide a potential therapeutic avenue for immunotherapies.

IMMUNITY (2021)

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Article Chemistry, Multidisciplinary

Glycosylation of PAMAM dendrimers significantly improves tumor macrophage targeting and specificity in glioblastoma

Rishi Sharma et al.

Summary: The research explores the use of sugar moieties conjugated to dendrimers for targeted therapy of glioblastoma and other cancers. Glucose modification significantly enhances targeting of tumor-associated macrophages and microglia, while galactose modification shifts targeting towards galectins on glioblastoma tumor cells.

JOURNAL OF CONTROLLED RELEASE (2021)

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Article Immunology

Blockade of the co-inhibitory molecule PD-1 unleashes ILC2-dependent antitumor immunity in melanoma

Nicolas Jacquelot et al.

Summary: ILC2s play a critical role in melanoma immunity by producing cytokines that enhance antitumor responses. High infiltration of ILC2s in melanoma is associated with good clinical prognosis, but their antitumor functions may be restricted by programmed cell death protein-1.

NATURE IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

The role of polyamines in gastric cancer

Kara M. McNamara et al.

Summary: Polyamine molecules play crucial roles in cellular growth and survival, affecting gastric immune cell and epithelial cell function. Dysregulation of polyamine metabolism is associated with Helicobacter pylori-induced gastritis and progression to gastric cancer, leading to promising potential in targeting the polyamine metabolic pathway for anticancer therapy.

ONCOGENE (2021)

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Review Oncology

The Metabolic Features of Tumor-Associated Macrophages: Opportunities for Immunotherapy?

Sonja S. Mojsilovic et al.

Summary: Apart from transformed cells, tumors consist of various cell types, with tumor-associated macrophages (TAMs) being the most abundant innate immune cells in the tumor microenvironment (TME). TAMs within the TME exhibit high plasticity and undergo specific functional metabolic alterations depending on the availability of tumor tissue oxygen and nutrients, further contributing to tumorigenesis and cancer progression.

ANALYTICAL CELLULAR PATHOLOGY (2021)

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Article Multidisciplinary Sciences

B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma

Ayana T. Ruffin et al.

Summary: The study suggests that enhancing TIL-B responses in HNSCC, particularly in HPV+ cases, could complement current T cell immunotherapies. The presence of tumor infiltrating B cells with GCs in TLS is associated with better survival outcomes in head and neck squamous cell carcinoma patients.

NATURE COMMUNICATIONS (2021)

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Review Oncology

Interleukin-25: New perspective and state-of-the-art in cancer prognosis and treatment approaches

Arezoo Gowhari Shabgah et al.

Summary: Imbalance of immune cell-derived factors like cytokines and chemokines play a central role in cancer progression. IL-25, a member of the IL-17 cytokine subfamily, has a dual role in cancer, serving both tumor supportive and tumor suppressive functions. Understanding the role of IL-25 and its receptor can aid in using IL-25 as a diagnostic and prognostic biomarker in cancer, as well as exploring IL-25-based therapeutic approaches for cancer inhibition.

CANCER MEDICINE (2021)

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Review Immunology

Targeting Aging: Lessons Learned From Immunometabolism and Cellular Senescence

Dominique E. Martin et al.

Summary: Immunometabolism plays a crucial role in aging, affecting immune cell activation and effector functions through metabolic pathways. It has been found that aging can impact the networks controlling immune cell metabolism, but further research is needed to fully understand these effects.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Immunology

The Recruitment of Neutrophils to the Tumor Microenvironment Is Regulated by Multiple Mediators

Shuvasree SenGupta et al.

Summary: Neutrophils play a crucial role in tumor progression and metastasis by sensing and migrating towards chemotactic factors released in the tumor microenvironment. The molecular mechanisms of how cancer cells secrete mediators to recruit neutrophils and the signaling network integration among mediators need further exploration for developing effective therapeutic strategies in cancer treatment.

FRONTIERS IN IMMUNOLOGY (2021)

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Review Oncology

Cancer metabolism: looking forward

Inmaculada Martinez-Reyes et al.

Summary: This Perspective discusses the main themes in cancer metabolism research, focusing on the relationship between tumour initiation and progression with metabolic reprogramming, as well as the importance of tumor microenvironment and metabolic regulation.

NATURE REVIEWS CANCER (2021)

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Review Immunology

Metabolic barriers to cancer immunotherapy

Kristin DePeaux et al.

Summary: The tumour microenvironment creates barriers that suppress immune responses, including physical barriers, recruitment of suppressive immune cells, and upregulation of inhibitory ligands on tumour cells. Therapies targeting metabolic restrictions in the tumour microenvironment show promise for combination therapies against various types of cancer.

NATURE REVIEWS IMMUNOLOGY (2021)

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Review Oncology

Systemic immunity in cancer

Kamir J. Hiam-Galvez et al.

Summary: Understanding systemic immune landscape beyond the tumour microenvironment is crucial in assessing the effectiveness of immunotherapy in cancer treatment. Despite the potential of immunotherapy to induce new immune responses, compromised immune responses in individuals with tumors may limit its efficacy.

NATURE REVIEWS CANCER (2021)

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Review Endocrinology & Metabolism

Metabolites and the tumour microenvironment: from cellular mechanisms to systemic metabolism

Ilaria Elia et al.

Summary: The article provides a detailed examination of the complexity of cellular metabolism within the tumor microenvironment, along with potential therapeutic intervention opportunities. Cancer cell metabolism and behavior are regulated by multiple factors, and the metabolic environment within the TME is influenced by various tiers. Understanding the interactions of these tiers reveals unique therapeutic potential for modulating the metabolic profile and function of all cells in the TME.

NATURE METABOLISM (2021)

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Review Immunology

Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity

Filippo Veglia et al.

Summary: MDSCs are pathologically activated cells with potent immunosuppressive activity, closely associated with poor clinical outcomes in diseases like cancer. Recent studies have identified key distinctions between MDSCs and classical neutrophils and monocytes, providing new insights into therapeutic targeting for cancer and autoimmune diseases through understanding their genomic and metabolic characteristics. Emerging data also suggest potential involvement of MDSCs in pregnancy, neonatal biology, and COVID-19.

NATURE REVIEWS IMMUNOLOGY (2021)

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Review Biochemistry & Molecular Biology

The role of polyamines in the regulation of macrophage polarization and function

Yvonne L. Latour et al.

AMINO ACIDS (2020)

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Article Cell Biology

Mitochondrial Integrity Regulated by Lipid Metabolism Is a Cell-Intrinsic Checkpoint for Treg Suppressive Function

Cameron S. Field et al.

CELL METABOLISM (2020)

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Editorial Material Immunology

IL-33-induced reactive oxygen species are required for optimal metabolic programming in group 2 innate lymphoid cells

Chaoyue Zheng et al.

CELLULAR & MOLECULAR IMMUNOLOGY (2020)

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Review Biochemistry & Molecular Biology

TGFβ-induced metabolic reprogramming during epithelial-to-mesenchymal transition in cancer

Wan Hua et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2020)

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Review Biochemistry & Molecular Biology

Chemokines and their receptors promoting the recruitment of myeloid-derived suppressor cells into the tumor

Bao-Hua Li et al.

MOLECULAR IMMUNOLOGY (2020)

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Article Multidisciplinary Sciences

B cells are associated with survival and immunotherapy response in sarcoma

Florent Petitprez et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Tertiary lymphoid structures improve immunotherapy and survival in melanoma

Rita Cabrita et al.

NATURE (2020)

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Article Multidisciplinary Sciences

B cells and tertiary lymphoid structures promote immunotherapy response

Beth A. Helmink et al.

NATURE (2020)

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Article Immunology

An intrinsic role of IL-33 in Treg cell-mediated tumor immunoevasion

Aikaterini Hatzioannou et al.

NATURE IMMUNOLOGY (2020)

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Article Immunology

CD36-mediated metabolic adaptation supports regulatory T cell survival and function in tumors

Haiping Wang et al.

NATURE IMMUNOLOGY (2020)

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Article Oncology

Improving cancer immunotherapy using nanomedicines: progress, opportunities and challenges

John D. Martin et al.

NATURE REVIEWS CLINICAL ONCOLOGY (2020)

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Review Oncology

The Engagement Between MDSCs and Metastases: Partners in Crime

Rosalinda Trovato et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Oncology

The hypoxic tumour microenvironment: A safe haven for immunosuppressive cells and a therapeutic barrier to overcome

Wai Hoong Chang et al.

CANCER LETTERS (2020)

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Article Cell Biology

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RIPK3 Orchestrates Fatty Acid Metabolism in Tumor-Associated Macrophages and Hepatocarcinogenesis

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CANCER IMMUNOLOGY RESEARCH (2020)

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Lipid-Droplet Formation Drives Pathogenic Group 2 Innate Lymphoid Cells in Airway Inflammation

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Targeting Mitochondria in Tumor-Associated Macrophages using a Dendrimer-Conjugated TSPO Ligand that Stimulates Antitumor Signaling in Glioblastoma

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CELLULAR IMMUNOLOGY (2020)

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Targeting glutamine metabolism enhances tumor-specific immunity by modulating suppressive myeloid cells

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Role of Proton-Coupled Monocarboxylate Transporters in Cancer: From Metabolic Crosstalk to Therapeutic Potential

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Innate lymphoid cell and adaptive immune cell cross-talk: A talk meant not to forget

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Antibiotic use and risk of colorectal cancer: a systematic review and dose-response meta-analysis

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The PD-1/PD-L1-Checkpoint Restrains T cell Immunity in Tumor-Draining Lymph Nodes

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Impaired mitochondrial oxidative phosphorylation limits the self-renewal of T cells exposed to persistent antigen

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Blockade of the AHR restricts a Treg-macrophage suppressive axis induced by L-Kynurenine

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The TLR9 ligand CpG ODN 2006 is a poor adjuvant for the induction of de novo CD8+ T-cell responses in vitro

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Cancer SLC43A2 alters T cell methionine metabolism and histone methylation

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Disturbed mitochondrial dynamics in CD8+TILs reinforce T cell exhaustion

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Lactate-Modulated Immunosuppression of Myeloid-Derived Suppressor Cells Contributes to the Radioresistance of Pancreatic Cancer

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IDO Expression in Cancer: Different Compartment, Different Functionality?

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Lactate Suppresses Macrophage Pro-Inflammatory Response to LPS Stimulation by Inhibition of YAP and NF-κB ActivationviaGPR81-Mediated Signaling

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Expression of Monocarboxylate Transporter 1 in Immunosuppressive Macrophages Is Associated With the Poor Prognosis in Breast Cancer

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Oncometabolites lactate and succinate drive pro-angiogenic macrophage response in tumors

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Lactate Limits T Cell Proliferation via the NAD(H) Redox State

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Human Tumor-Associated Macrophage and Monocyte Transcriptional Landscapes Reveal Cancer-Specific Reprogramming, Biomarkers, and Therapeutic Targets

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Macrophage-Released Pyrimidines Inhibit Gemcitabine Therapy in Pancreatic Cancer

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Age-related changes in B cell metabolism

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Immature Low-Density Neutrophils Exhibit Metabolic Flexibility that Facilitates Breast Cancer Liver Metastasis

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Lipid Metabolic Pathways Confer the Immunosuppressive Function of Myeloid-Derived Suppressor Cells in Tumor

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Lactate Induces Pro-tumor Reprogramming in Intratumoral Plasmacytoid Dendritic Cells

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Peripheral Innate Lymphoid Cells Are Increased in First Line Metastatic Colorectal Carcinoma Patients: A Negative Correlation With Th1 Immune Responses

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The Obese Liver Environment Mediates Conversion of NK Cells to a Less Cytotoxic ILC1-Like Phenotype

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Invariant NKT cells facilitate cytotoxic T-cell activation via direct recognition of CD1d on T cells

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Circular ecDNA promotes accessible chromatin and high oncogene expression

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Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion

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Dendritic Cells Require PINK1-Mediated Phosphorylation of BCKDE1 a to Promote Fatty Acid Oxidation for Immune Function

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Tumor Microenvironment Remodeling by Intratumoral Oncolytic Vaccinia Virus Enhances the Efficacy of Immune-Checkpoint Blockade

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Human Tolerogenic Dendritic Cells Regulate Immune Responses through Lactate Synthesis

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Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis

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A RIPK3-PGE(2) Circuit Mediates Myeloid-Derived Suppressor Cell-Potentiated Colorectal Carcinogenesis

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Increased Tumor Glycolysis Characterizes Immune Resistance to Adoptive T Cell Therapy

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CURRENT OPINION IN IMMUNOLOGY (2018)

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T Cell Receptor-Regulated TGF-β Type I Receptor Expression Determines T Cell Quiescence and Activation

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B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells

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E3 Ligase VHL Promotes Group 2 Innate Lymphoid Cell Maturation and Function via Glycolysis Inhibition and Induction of Interleukin-33 Receptor

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Paracrine Wnt5a-beta-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization

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IMMUNITY (2018)

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INTERNATIONAL IMMUNOPHARMACOLOGY (2018)

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B1a B cells require autophagy for metabolic homeostasis and self-renewal

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Canonical TGF-β Signaling Pathway Represses Human NK Cell Metabolism

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JOURNAL OF IMMUNOLOGY (2018)

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Regulation of B cell fate, survival, and function by mitochondria and autophagy

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MITOCHONDRION (2018)

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Fatty acid oxidation contributes to IL-1β secretion in M2 macrophages and promotes macrophage-mediated tumor cell migration

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MOLECULAR IMMUNOLOGY (2018)

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Review Biochemistry & Molecular Biology

Dendritic cells in sepsis: Potential immunoregulatory cells with therapeutic potential

V Kumar

MOLECULAR IMMUNOLOGY (2018)

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Review Immunology

Myeloid-derived suppressor cells coming of age

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NATURE IMMUNOLOGY (2018)

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Review Immunology

Metabolic Links between Plasma Cell Survival, Secretion, and Stress

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Glycolytic metabolism is essential for CCR7 oligomerization and dendritic cell migration

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NATURE COMMUNICATIONS (2018)

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Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments

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CELL REPORTS (2018)

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Article Cell Biology

Isotope Tracing of Human Clear Cell Renal Cell Carcinomas Demonstrates Suppressed Glucose Oxidation In Vivo

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CELL METABOLISM (2018)

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Review Cell Biology

Immunometabolism of T cells and NK cells: metabolic control of effector and regulatory function

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INFLAMMATION RESEARCH (2018)

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Cutting Edge: TGF-β and Phosphatidylinositol 3-Kinase Signals Modulate Distinct Metabolism of Regulatory T Cell Subsets

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JOURNAL OF IMMUNOLOGY (2018)

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Metabolic and Transcriptional Modules Independently Diversify Plasma Cell Lifespan and Function

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CELL REPORTS (2018)

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Revisiting the Warburg Effect: Some Tumors Hold Their Breath

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CELL METABOLISM (2018)

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Review Biochemistry & Molecular Biology

Effects of tumor metabolic microenvironment on regulatory T cells

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MOLECULAR CANCER (2018)

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Unique pattern of neutrophil migration and function during tumor progression

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NATURE IMMUNOLOGY (2018)

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Mitochondrial p32/C1qbp Is a Critical Regulator of Dendritic Cell Metabolism and Maturation

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CELL REPORTS (2018)

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Review Immunology

The Pro-tumorigenic IL-33 Involved in Antitumor Immunity: A Yin and Yang Cytokine

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FRONTIERS IN IMMUNOLOGY (2018)

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Article Immunology

In vitro and in vivo Effects of Lactate on Metabolism and Cytokine Production of Human Primary PBMCs and Monocytes

Jacqueline M. Ratter et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Review Oncology

The Role of Type 1 Conventional Dendritic Cells in Cancer Immunity

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TRENDS IN CANCER (2018)

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Review Cell Biology

Targeting Tumor-Associated Macrophages as a Potential Strategy to Enhance the Response to Immune Checkpoint Inhibitors

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FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2018)

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Initial B Cell Activation Induces Metabolic Reprogramming and Mitochondrial Remodeling

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ISCIENCE (2018)

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Human Innate Lymphoid Cell Subsets Possess Tissue-Type Based Heterogeneity in Phenotype and Frequency

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IMMUNITY (2017)

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Neutrophils in Homeostasis, Immunity, and Cancer

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Efferocytosis of dying cells differentially modulate immunological outcomes in tumor microenvironment

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ILC2-modulated T cell-to-MDSC balance is associated with bladder cancer recurrence

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Review Biochemistry & Molecular Biology

AMPK: Mechanisms of Cellular Energy Sensing and Restoration of Metabolic Balance

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MOLECULAR CELL (2017)

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Tumour-associated macrophages as treatment targets in oncology

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IL-12p35 induces expansion of IL-10 and IL-35-expressing regulatory B cells and ameliorates autoimmune disease

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Suppressive IL-17A+Foxp3+ and ex-Th17 IL-17AnegFoxp3+ Treg cells are a source of tumour-associated Treg cells

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Tumour-derived PGD2 and NKp30-B7H6 engagement drives an immunosuppressive ILC2-MDSC axis

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FRONTIERS IN IMMUNOLOGY (2017)

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Exogenous lipid uptake induces metabolic and functional reprogramming of tumor-associated myeloid-derived suppressor cells

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ONCOIMMUNOLOGY (2017)

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Article Oncology

Enhancing CD8+ T Cell Fatty Acid Catabolism within a Metabolically Challenging Tumor Microenvironment Increases the Efficacy of Melanoma Immunotherapy

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Article Biochemistry & Molecular Biology

Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy

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CELL (2017)

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Article Cell Biology

Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses

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CELL METABOLISM (2017)

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Tumor immunoevasion by the conversion of effector NK cells into type 1 innate lymphoid cells

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NATURE IMMUNOLOGY (2017)

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Review Biochemistry & Molecular Biology

MYC and HIF in shaping immune response and immune metabolism

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CYTOKINE & GROWTH FACTOR REVIEWS (2017)

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Foxp3 Reprograms T Cell Metabolism to Function in Low-Glucose, High-Lactate Environments

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CELL METABOLISM (2017)

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Meeting Abstract Oncology

A first-in-human first-in-class (FIC) trial of the monocarboxylate transporter 1 (MCT1) inhibitor AZD3965 in patients with advanced solid tumours.

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JOURNAL OF CLINICAL ONCOLOGY (2017)

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Review Biochemistry & Molecular Biology

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Gsk3 is a metabolic checkpoint regulator in B cells

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NATURE IMMUNOLOGY (2017)

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Tissue Immunometabolism: Development, Physiology, and Pathobiology

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Immunometabolism governs dendritic cell and macrophage function

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PD-1 expression on dendritic cells suppresses CD8(+) T cell function and antitumor immunity

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ONCOIMMUNOLOGY (2016)

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Transcriptional Control of Dendritic Cell Development

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ANNUAL REVIEW OF IMMUNOLOGY, VOL 34 (2016)

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Review Biochemistry & Molecular Biology

Glycolysis inhibition as a cancer treatment and its role in an anti-tumour immune response

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BIOCHIMICA ET BIOPHYSICA ACTA-REVIEWS ON CANCER (2016)

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Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche

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CELL (2016)

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L-Arginine Modulates T Cell Metabolism and Enhances Survival and Anti-tumor Activity

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Lactate Wreaks Havoc on Tumor-Infiltrating T and NK Cells

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Cell Metabolism (2016)

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Macrophage Metabolism Shapes Angiogenesis in Tumors

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LDHA-Associated Lactic Acid Production Blunts Tumor Immunosurveillance by T and NK Cells

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Cell Metabolism (2016)

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HAEMATOLOGICA (2016)

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The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction

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Mitochondrial Pyruvate Import Promotes Long-Term Survival of Antibody-Secreting Plasma Cells

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Metabolic Reprogramming Mediated by the mTORC2-IRF4 Signaling Axis Is Essential for Macrophage Alternative Activation

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Critical role of fatty acid metabolism in ILC2-mediated barrier protection during malnutrition and helminth infection

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Foxp3 and Toll-like receptor signaling balance Treg cell anabolic metabolism for suppression

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ONCOTARGET (2016)

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HAEMATOLOGICA (2016)

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Acquisition and Presentation of Tumor Antigens by Dendritic Cells

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High Mitochondrial Respiration and Glycolytic Capacity Represent a Metabolic Phenotype of Human Tolerogenic Dendritic Cells

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Activation-Specific Metabolic Requirements for NK Cell IFN-γ Production

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Inflammatory ILC2 cells: disguising themselves as progenitors?

Shigeo Koyasu

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CD47 blockade as another immune checkpoint therapy for cancer

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CD47 blockade triggers T cell-mediated destruction of immunogenic tumors

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Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation

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NCR+ILC3 concentrate in human lung cancer and associate with intratumoral lymphoid structures

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M-CSF from Cancer Cells Induces Fatty Acid Synthase and PPARβ/δ Activation in Tumor Myeloid Cells, Leading to Tumor Progression

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Lactate Regulates Metabolic and Proinflammatory Circuits in Control of T Cell Migration and Effector Functions

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Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation

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Melanoma-Derived Wnt5a Promotes Local Dendritic-Cell Expression of IDO and Immunotolerance: Opportunities for Pharmacologic Enhancement of Immunotherapy

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Inhibition of Fatty Acid Oxidation Modulates Immunosuppressive Functions of Myeloid-Derived Suppressor Cells and Enhances Cancer Therapies

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IL-25-responsive, lineage-negative KLRG1hi cells are multipotential 'inflammatory' type 2 innate lymphoid cells

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NATURE IMMUNOLOGY (2015)

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Network Integration of Parallel Metabolic and Transcriptional Data Reveals Metabolic Modules that Regulate Macrophage Polarization

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NATURE REVIEWS IMMUNOLOGY (2015)

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Presence of B Cells in Tertiary Lymphoid Structures Is Associated with a Protective Immunity in Patients with Lung Cancer

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Fatty acid oxidation is dispensable for human macrophage IL-4-induced polarization

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Hypoxia-inducible factor 2α regulates key neutrophil functions in humans, mice, and zebrafish

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Activity of the Monocarboxylate Transporter 1 Inhibitor AZD3965 in Small Cell Lung Cancer

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CLINICAL CANCER RESEARCH (2014)

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Inflammatory T Cell Responses Rely on Amino Acid Transporter ASCT2 Facilitation of Glutamine Uptake and mTORC1 Kinase Activation

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IMMUNOLOGY LETTERS (2014)

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T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow

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PD-L1 is a novel direct target of HIF-1α., and its blockade under hypoxia enhanced MDSC-mediated T cell activation

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mTORC1-Dependent Metabolic Reprogramming Is a Prerequisite for NK Cell Effector Function

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TLR-driven early glycolytic reprogramming via the kinases TBK1-IKKε supports the anabolic demands of dendritic cell activation

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The metabolic checkpoint kinase mTOR is essential for IL-15 signaling during the development and activation of NK cells

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Regulatory B cells are induced by gut microbiota-driven interleukin-1β and interleukin-6 production

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Interleukin-35 induces regulatory B cells that suppress autoimmune disease

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NATURE MEDICINE (2014)

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Tumoricidal activity of human dendritic cells

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TRENDS IN IMMUNOLOGY (2014)

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Polyamine-Blocking Therapy Reverses Immunosuppression in the Tumor Microenvironment

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CANCER IMMUNOLOGY RESEARCH (2014)

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Polarization of ILC2s in Peripheral Blood Might Contribute to Immunosuppressive Microenvironment in Patients with Gastric Cancer

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Metabolic Regulation of T Lymphocytes

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ANNUAL REVIEW OF IMMUNOLOGY, VOL 31 (2013)

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Tumor Microenvironmental Conversion of Natural Killer Cells into Myeloid-Derived Suppressor Cells

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CANCER RESEARCH (2013)

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Posttranscriptional Control of T Cell Effector Function by Aerobic Glycolysis

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CELL (2013)

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Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer

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IMMUNITY (2013)

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Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

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Role of Fatty-Acid Synthesis in Dendritic Cell Generation and Function

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JOURNAL OF IMMUNOLOGY (2013)

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Tumor-Derived Lactate Modifies Antitumor Immune Response: Effect on Myeloid-Derived Suppressor Cells and NK Cells

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JOURNAL OF IMMUNOLOGY (2013)

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Type 2 innate lymphoid cells control eosinophil homeostasis

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Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation

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NATURE IMMUNOLOGY (2013)

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Innate and adaptive immune cells in the tumor microenvironment

Thomas F. Gajewski et al.

NATURE IMMUNOLOGY (2013)

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Adenosine as an endogenous immunoregulator in cancer pathogenesis: where to go?

V. Kumar

PURINERGIC SIGNALLING (2013)

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IRE1: ER stress sensor and cell fate executor

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TRENDS IN CELL BIOLOGY (2013)

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B regulatory cells in cancer

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TRENDS IN IMMUNOLOGY (2013)

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Tumor-derived lactate and myeloid-derived suppressor cells Linking metabolism to cancer immunology

Zaheed Husain et al.

ONCOIMMUNOLOGY (2013)

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Neutrophil recruitment and function in health and inflammation

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NATURE REVIEWS IMMUNOLOGY (2013)

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Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes

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NATURE REVIEWS IMMUNOLOGY (2013)

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Decisions About Dendritic Cells: Past, Present, and Future

Ralph M. Steinman

ANNUAL REVIEW OF IMMUNOLOGY, VOL 30 (2012)

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L-glutamine is a key parameter in the immunosuppression phenomenon

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2012)

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Immunosuppressive activity enhances central carbon metabolism and bioenergetics in myeloid-derived suppressor cells in vitro models

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BMC CELL BIOLOGY (2012)

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The Transcription Factors T-bet and Eomes Control Key Checkpoints of Natural Killer Cell Maturation

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IMMUNITY (2012)

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Activated CD69+ T Cells Foster Immune Privilege by Regulating IDO Expression in Tumor-Associated Macrophages

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JOURNAL OF IMMUNOLOGY (2012)

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MicroRNA-494 Is Required for the Accumulation and Functions of Tumor-Expanded Myeloid-Derived Suppressor Cells via Targeting of PTEN

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JOURNAL OF IMMUNOLOGY (2012)

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Pivotal Advance: Arginase-1-independent polyamine production stimulates the expression of IL-4-induced alternatively activated macrophage markers while inhibiting LPS-induced expression of inflammatory genes

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JOURNAL OF LEUKOCYTE BIOLOGY (2012)

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Article Immunology

The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry

David Dominguez-Sola et al.

NATURE IMMUNOLOGY (2012)

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Review Biochemistry & Molecular Biology

Hallmarks of cancer: of all cancer cells, all the time?

Sebastien L. Floor et al.

TRENDS IN MOLECULAR MEDICINE (2012)

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Aging-associated changes in hematopoiesis and leukemogenesis: What's the connection?

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AGING-US (2011)

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Natural Innate and Adaptive Immunity to Cancer

Matthew D. Vesely et al.

ANNUAL REVIEW OF IMMUNOLOGY, VOL 29 (2011)

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Lactate: A Metabolic Key Player in Cancer

Franziska Hirschhaeuser et al.

CANCER RESEARCH (2011)

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Hallmarks of Cancer: The Next Generation

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CELL (2011)

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The Transcription Factor Myc Controls Metabolic Reprogramming upon T Lymphocyte Activation

Ruoning Wang et al.

IMMUNITY (2011)

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The mechanisms by which polyamines accelerate tumor spread

Kuniyasu Soda

JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH (2011)

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HIF1α-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells

Lewis Z. Shi et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2011)

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Cutting Edge: Distinct Glycolytic and Lipid Oxidative Metabolic Programs Are Essential for Effector and Regulatory CD4+ T Cell Subsets

Ryan D. Michalek et al.

JOURNAL OF IMMUNOLOGY (2011)

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Compartmentalization of the nucleus

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TRENDS IN CELL BIOLOGY (2011)

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Review Oncology

Regulation of cancer cell metabolism

Rob A. Cairns et al.

NATURE REVIEWS CANCER (2011)

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Toll-like receptor-induced changes in glycolytic metabolism regulate dendritic cell activation

Connie M. Krawczyk et al.

BLOOD (2010)

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HIF-1α regulates function and differentiation of myeloid-derived suppressor cells in the tumor microenvironment

Cesar A. Corzo et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2010)

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An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells

Joshua D. Mezrich et al.

JOURNAL OF IMMUNOLOGY (2010)

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Article Immunology

B Cells Are Required for Optimal CD4+ and CD8+ T Cell Tumor Immunity: Therapeutic B Cell Depletion Enhances B16 Melanoma Growth in Mice

David J. DiLillo et al.

JOURNAL OF IMMUNOLOGY (2010)

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Targeting dendritic cell metabolism in cancer

Laurence Zitvogel et al.

NATURE MEDICINE (2010)

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Article Biochemistry & Molecular Biology

Lipid accumulation and dendritic cell dysfunction in cancer

Donna L. Herber et al.

NATURE MEDICINE (2010)

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The polarization of immune cells in the tumour environment by TGFβ

Richard A. Flavell et al.

NATURE REVIEWS IMMUNOLOGY (2010)

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Polarization of Tumor-Associated Neutrophil Phenotype by TGF-β: N1 versus N2 TAN

Zvi G. Fridlender et al.

CANCER CELL (2009)

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Adenosine: An endogenous modulator of innate immune system with therapeutic potential

Vijay Kumar et al.

EUROPEAN JOURNAL OF PHARMACOLOGY (2009)

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Article Immunology

The mTOR Kinase Differentially Regulates Effector and Regulatory T Cell Lineage Commitment

Greg M. Delgoffe et al.

IMMUNITY (2009)

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Article Immunology

PD-L1 regulates the development, maintenance, and function of induced regulatory T cells

Loise M. Francisco et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2009)

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Understanding the Warburg Effect: The Metabolic Requirements of Cell Proliferation

Matthew G. Vander Heiden et al.

SCIENCE (2009)

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Review Immunology

Myeloid-derived suppressor cells as regulators of the immune system

Dmitry I. Gabrilovich et al.

NATURE REVIEWS IMMUNOLOGY (2009)

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Article Hematology

Adenosine receptors in regulation of dendritic cell differentiation and function

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BLOOD (2008)

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Review Hematology

B lymphocytes: how they develop and function

Tucker W. LeBien et al.

BLOOD (2008)

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Article Immunology

Glucose deprivation inhibits multiple key gene expression events and effector functions in CD8+ T cells

Candace M. Cham et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2008)

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Role of Bv8 in neutrophil-dependent angiogenesis in a transgenic model of cancer progression

Farbod Shojaei et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Plasmacytoid dendritic cells from mouse tumor-draining lymph nodes directly activate mature Tregs via indoleamine 2,3-dioxygenase

Madhav D. Sharma et al.

JOURNAL OF CLINICAL INVESTIGATION (2007)

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Review Oncology

Metabolic mechanisms of cancer-induced inhibition of immune responses

Antonella Viola et al.

SEMINARS IN CANCER BIOLOGY (2007)

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Immune surveillance of tumors

Jeremy B. Swann et al.

JOURNAL OF CLINICAL INVESTIGATION (2007)

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Inhibitory effect of tumor cell-derived lactic acid on human T cells

Karin Fischer et al.

BLOOD (2007)

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Article Immunology

Regulation of carcinogenesis by IL-5 and CCL11: A potential role for eosinophils in tumor immune surveillance

Ljubov Simson et al.

JOURNAL OF IMMUNOLOGY (2007)

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Article Immunology

Cell-autonomous control of interferon type I expression by indoleamine 2,3-dioxygenase in regulatory CD19(+) dendritic cells

Anna K. Manlapat et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2007)

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Article Immunology

Tryptophan catabolism generates autoimmune-preventive regulatory T cells

Francesca Fallarino et al.

TRANSPLANT IMMUNOLOGY (2006)

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Understanding and exploiting the endogenous interleukin-10/STAT3-mediated anti-inflammatory response

Peter J. Murray

CURRENT OPINION IN PHARMACOLOGY (2006)

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Article Immunology

The combined effects of tryptophan starvation and tryptophan catabolites down-regulate T cell receptor ζ-chain and induce a regulatory phenotype in naive T cells

Francesca Fallarino et al.

JOURNAL OF IMMUNOLOGY (2006)

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Article Immunology

The Noxa/Mcl-1 axis regulates susceptibility to apoptosis under glucose limitation in dividing T cells

Nuno L. Alves et al.

IMMUNITY (2006)

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Acid-mediated tumor invasion: a multidisciplinary study

RA Gatenby et al.

CANCER RESEARCH (2006)

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Article Immunology

Systemic application of CpG-rich DNA suppresses adaptive T cell immunity via induction of IDO

G Wingender et al.

EUROPEAN JOURNAL OF IMMUNOLOGY (2006)

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Review Immunology

Regulation of immune responses by L- arginine metabolism

V Bronte et al.

NATURE REVIEWS IMMUNOLOGY (2005)

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Myc stimulates nuclearly encoded mitochondrial genes and mitochondrial biogenesis

F Li et al.

MOLECULAR AND CELLULAR BIOLOGY (2005)

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Interchromosomal associations between alternatively expressed loci

CG Spilianakis et al.

NATURE (2005)

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GCN2 kinase in T cells mediates proliferative arrest and anergy induction in response to indoleamine 2,3-dioxygenase

DH Munn et al.

IMMUNITY (2005)

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De novo carcinogenesis promoted by chronic inflammation is B lymphocyte dependent

KE de Visser et al.

CANCER CELL (2005)

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Hypoxia-induced neutrophil survival is mediated by HIF-1α-dependent NF-κB activity

SR Walmsley et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2005)

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Drug-induced increase of carcinoembryonic antigen expression in cancer cells

A Aquino et al.

PHARMACOLOGICAL RESEARCH (2004)

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Lymphoid follicle destruction and immunosuppression after repeated CpG oligodeoxynucleotide administration

M Heikenwalder et al.

NATURE MEDICINE (2004)

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Prognostic significance of tissue transglutaminase in drug resistant and metastatic breast cancer

K Mehta et al.

CLINICAL CANCER RESEARCH (2004)

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Hypoxia-inducible factor I (HIF-1) in cancer

M Quintero et al.

EJSO (2004)

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XBP1: a link between the unfolded protein response, lipid biosynthesis, and biogenesis of the endoplasmic reticulum

R Sriburi et al.

JOURNAL OF CELL BIOLOGY (2004)

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Long-range intrachromosomal interactions in the T helper type 2 cytokine locus

CG Spilianakis et al.

NATURE IMMUNOLOGY (2004)

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Targeting HIF-1 for cancer therapy

GL Semenza

NATURE REVIEWS CANCER (2003)

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Applying the principles of stem-cell biology to cancer

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NATURE REVIEWS CANCER (2003)

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Polyamine levels of human colorectal adenocarcinomas are correlated with tumor stage and grade

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INTERNATIONAL JOURNAL OF COLORECTAL DISEASE (2002)

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Impaired perforin-dependent NK cell cytotoxicity and proliferative activity of peripheral blood T cells is associated with metastatic melanoma

V Jovic et al.

TUMORI JOURNAL (2001)

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Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population

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LANCET (2000)

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CD91: a receptor for heat shock protein gp96

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NATURE IMMUNOLOGY (2000)

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The hallmarks of cancer

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CELL (2000)

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