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Tumour-associated macrophages: versatile players in the tumour microenvironment

FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY (2023)

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Article Medicine, Research & Experimental

M2 tumor-associated macrophage mediates the maintenance of stemness to promote cisplatin resistance by secreting TGF-beta 1 in esophageal squamous cell carcinoma

Kaige Yang et al.

Summary: This study found that M2 tumor-associated macrophages (M2-TAMs) promote stemness characteristics and induce cisplatin resistance in esophageal squamous cell carcinoma (ESCC) cells by secreting TGF-beta 1. This finding helps to understand the mechanism of chemotherapy resistance in ESCC.

JOURNAL OF TRANSLATIONAL MEDICINE (2023)

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Review Biochemistry & Molecular Biology

CAR-cell therapy in the era of solid tumor treatment: current challenges and emerging therapeutic advances

Karama Makni Maalej et al.

Summary: In the last decade, Chimeric Antigen Receptor (CAR)-T cell therapy has shown efficacy in treating hematological malignancies, but its value in solid tumors remains inconclusive. The limitations of CAR-T cell therapy in solid tumors include limited tumor trafficking and infiltration, an immunosuppressive tumor microenvironment, and adverse events. CAR-NK and CAR-M cells have been introduced as alternative immunotherapies for solid tumors, with potential advantages such as no HLA compatibility requirement and limited toxicity for CAR-NK cells, and capabilities of phagocytosis, tumor-antigen presentation, and broad tumor infiltration for CAR-M cells. Prospective solutions, such as combination therapies, could enhance the efficacy of CAR-cell immunotherapy.

MOLECULAR CANCER (2023)

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Article Clinical Neurology

Increased Circulating Chemokines and Macrophage Recruitment in Growing Vestibular Schwannomas

Cathal John Hannan et al.

Summary: There is evidence that macrophage infiltration in the tumor microenvironment promotes the growth of vestibular schwannoma (VS). The efficacy of bevacizumab in NF2-associated VS demonstrates the value of targeting the microvascular tumor microenvironment, and tumor-associated macrophages (TAMs) may represent another druggable target.

NEUROSURGERY (2023)

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Article Multidisciplinary Sciences

ROCK2 interacts with p22phox to phosphorylate p47phox and to control NADPH oxidase activation in human monocytes

Asma Tlili et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2023)

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Article Oncology

Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity

Marc Pfefferle et al.

Summary: The study revealed that CD40 signaling in Clec4f(+) Kupffer cells triggers anti-CD40 antibody-induced liver toxicity. However, controlled erythrophagocytosis and the linked anti-inflammatory signaling by the endogenous metabolite heme can be exploited to reprogram liver macrophages and prevent necroinflammatory liver disease caused by high-dose administration of anti-CD40 antibodies.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

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Article Oncology

Spatially resolved multimarker evaluation of CD274 (PD-L1)/PDCD1 (PD-1) immune checkpoint expression and macrophage polarisation in colorectal cancer

Hanna Elomaa et al.

Summary: The expression patterns and prognostic significance of PD-L1 and PD-1 in the colorectal cancer microenvironment are inadequately characterised. This study found that PD-L1(+) macrophages and PD-1(+) T cells were associated with better clinical outcomes in colorectal cancer patients. These findings enhance the understanding of immune checkpoints in the tumor microenvironment and could contribute to the development of improved immunotherapies.

BRITISH JOURNAL OF CANCER (2023)

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Article Oncology

Neutralizing IL-8 potentiates immune checkpoint blockade efficacy for glioma

Haofei Liu et al.

Summary: By examining the microenvironment in glioma, we find that tumor-infiltrating T cells are mainly located in the perivascular cuffs and express high levels of CCR5, CXCR3, and PD-1. Analysis of T cell clustering and TCR clone expansion reveals that potential tumor-killing T cells belong to pre-exhausted/exhausted and effector CD8+ T subsets, as well as cytotoxic CD4+ T subsets. In addition, a distinctive subpopulation of CD4+ T cells with innate-like features and preferential interleukin-8 (IL-8) expression is identified. We demonstrate that IL-8, along with myeloid and tumor cells, coordinates myeloid-derived suppressor cell infiltration and angiogenesis, leading to enhanced tumor growth but reduced efficacy of immune checkpoint blockade therapy. Blockade of IL-8 or its receptor CXCR1/2 unleashes the antitumor immunity mediated by anti-PD-1. Therefore, IL-8 is highlighted as a potential immunotherapy target for glioma.

CANCER CELL (2023)

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Article Biochemistry & Molecular Biology

PDLIM2 can inactivate the TGF-β/Smad pathway to inhibit the malignant behavior of ovarian cancer cells

Weiqin Lv et al.

Summary: The expression of PDLIM2 is low in ovarian cancer. Upregulation of PDLIM2 can attenuate the proliferation, migration, and invasion of ovarian cancer cells by inactivating the TGF-beta/Smad pathway. Therefore, PDLIM2 may be a useful target for ovarian cancer treatment.

CELL BIOCHEMISTRY AND FUNCTION (2023)

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Review Cell & Tissue Engineering

Advancing cell-based cancer immunotherapy through stem cell engineering

Yan-Ruide Li et al.

Summary: Advancements in cell-based therapy, especially CAR-T cell therapy, have revolutionized the treatment of blood cancers. However, autologous CAR-T therapies face obstacles such as high costs, manufacturing difficulties, and limited effectiveness against solid tumors. By utilizing gene editing and culture techniques, engineered stem cells offer a promising solution to these challenges in cell therapy.

CELL STEM CELL (2023)

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Correction Oncology

miR-382 inhibits breast cancer progression and metastasis by affecting the M2 polarization of tumor-associated macrophages by targeting PGC-1α (vol 61, 126, 2022)

Hua Zhou et al.

INTERNATIONAL JOURNAL OF ONCOLOGY (2023)

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Article Cell Biology

Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells

Remi Mascarau et al.

Summary: Mascarau et al. demonstrate the relevance of HIV-1 infection of tissue-resident macrophages by fusion with infected CD4(+) T cells and show that this process is modulated by the macrophage activation state and is under the control of the CD81/RhoA/Myosin axis. Macrophages play a critical role in HIV-1 pathogenesis and serve as major viral reservoirs. Understanding macrophage infection, especially in tissue macrophages, is crucial for understanding the persistence of the virus in patients.

JOURNAL OF CELL BIOLOGY (2023)

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Article Chemistry, Multidisciplinary

Engineered macrophages acting as a trigger to induce inflammation only in tumor tissues

Kenta Tanito et al.

Summary: In this study, engineered macrophages called MacTrigger were used to induce an inflammatory environment specifically in tumor tissues, leading to potent anti-tumor effects. MacTrigger utilized two unique functions of macrophages: their ability to migrate to tumor tissues and polarization into anti-inflammatory M2 phenotype when in the presence of tumor tissues. The results showed that MacTrigger could induce inflammation in tumor tissues, significantly inhibit tumor growth, and increase the ratio of M1 phenotype to M2 phenotype, as well as the presence of natural killer cells and CD8(+)T cells in tumor tissues.

JOURNAL OF CONTROLLED RELEASE (2023)

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Review Biochemistry & Molecular Biology

NK cells are never alone: crosstalk and communication in tumour microenvironments

Yongqiang Zhou et al.

Summary: Immune escape is a characteristic of cancer, and the tumor microenvironment plays a role in inhibiting the effectiveness of natural killer cell-based immunotherapy. Understanding the interaction between natural killer cells and the tumor microenvironment can help improve immunotherapy strategies.

MOLECULAR CANCER (2023)

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Review Biochemistry & Molecular Biology

Cross-talk between cancer stem cells and immune cells: potential therapeutic targets in the tumor immune microenvironment

Bo Wu et al.

Summary: Ongoing research has revealed that the existence of cancer stem cells (CSCs) is a major obstacle in current cancer therapy. CSCs play a significant role in tumor progression, recurrence, and chemoresistance due to their stemness characteristics. CSCs interact with the tumor microenvironment through complex mechanisms, and also engage in interactions with immune cells and molecules to protect themselves against immune clearance. Understanding these interactions may provide novel therapeutic approaches to cancer.

MOLECULAR CANCER (2023)

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Article Multidisciplinary Sciences

Neoantigen-targeted CD8+ T cell responses with PD-1 blockade therapy

Cristina Puig-Saus et al.

Summary: We isolated neoantigen-specific T cells from blood and tumors of melanoma patients using newly developed technologies. Multiple T cell clones with different neoTCR sequences recognized a limited number of mutations in samples from patients with clinical responses. These recurring neoTCR clonotypes were detected in blood and tumors over time. Patients with no response also showed neoantigen-specific T cell responses, but with lower TCR polyclonality and were not recurrently detected in sequential samples. Reconstructing neoTCRs in donor T cells demonstrated specific recognition and cytotoxicity to patient-matched melanoma cell lines.

NATURE (2023)

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Review Cell Biology

The role of N-glycosylation modification in the pathogenesis of liver cancer

Mengyu Hu et al.

Summary: N-glycosylation is a common protein modification that plays a vital role in physiological processes, but abnormal N-glycan modifications are closely linked to various diseases, including malignancy and tumor progression. Understanding the heterogeneity and biological functions of glycans in liver cancer patients can enhance our understanding of the molecular mechanisms of liver injury and hepatocarcinogenesis.

CELL DEATH & DISEASE (2023)

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Article Multidisciplinary Sciences

Smad3 is essential for polarization of tumor-associated neutrophils in non-small cell lung carcinoma

Jeff Yat-Fai Chung et al.

Summary: In this study, the researchers found that phenotype and function of tumor-associated neutrophils (TANs) are influenced by the microenvironment, resulting in different impact on tumor development as N1 or N2 state. They discovered that Smad3 activation is negatively correlated with N2 state and patient survival in NSCLC patients. In preclinical lung cancer models, targeting Smad3 reprogrammed TANs to an antitumor state (N1), suppressing tumor growth. Mechanistically, Smad3 regulated the maturity of TANs and maintained the N2 state through controlling genes related to cell fate determination. Thus, the findings suggest that Smad3 signaling could be a therapeutic target for cancer immunotherapy.

NATURE COMMUNICATIONS (2023)

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Article Cell Biology

Oral feeding of nanoplastics affects brain function of mice by inducing macrophage IL-1 signal in the intestine

Qianyu Yang et al.

Summary: This study investigates the effects of nanoplastics (NPs) on the gut immune landscape and brain immunity. The results demonstrate that NPs have a stronger impact on gut macrophage activation compared to microplastics (MPs). Moreover, NPs induce the reprogramming of gut interleukin-1 (IL-1)-producing macrophages through lysosomal damage, leading to microglial activation and Th17 differentiation in the brain, resulting in cognitive decline and short-term memory impairment in NP-fed mice. These findings provide insight into the mechanism of the gut-brain axis and highlight the global importance of addressing plastic pollution.

CELL REPORTS (2023)

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Article Biology

Transferred mitochondria accumulate reactive oxygen species, promoting proliferation

Chelsea U. Kidwell et al.

Summary: Recent studies have found that mitochondrial transfer between cells can impact cellular and tissue homeostasis. While most previous research focused on the transfer of functional mitochondria to cells with damaged networks, this study reveals that dysfunctional mitochondria can also be transferred between cells with functioning networks. The transfer of dysfunctional macrophage mitochondria to cancer cells leads to an accumulation of reactive oxygen species, activating signaling pathways that promote cancer cell proliferation. These findings provide insights into how transferred mitochondria can drive sustained behavioral changes in recipient cells.

ELIFE (2023)

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Article Immunology

PD-1 and CTLA-4 exert additive control of effector regulatory T cells at homeostasis

Joseph A. Pereira et al.

Summary: At homeostasis, a significant proportion of activated Foxp3(+) T regulatory cells (T-regs), called eT(regs), co-express higher levels of PD-1 and CTLA-4. Short term blockade of PD-1 or CTLA-4 pathways increases eT(reg) populations, while combined blockade of both pathways has an additive effect. Mechanistically, combined blockade decreases suppressive phospho-SHP2 Y580 in eT(reg) cells, leading to increased proliferation, enhanced IL-10 production, and reduced expression of CD80 and MHC-II in dendritic cells and macrophages. Therefore, targeting PD-1 and CTLA-4 pathways in T-reg cells can be useful in modulating inflammation.

FRONTIERS IN IMMUNOLOGY (2023)

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Article Immunology

Surfactant protein A alters endosomal trafficking of influenza A virus in macrophages

Eric Yau et al.

Frontiers in Immunology (2023)

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Article Oncology

Invasive margin tissue-resident macrophages of high CD163 expression impede responses to T cell-based immunotherapy

Marit J. van Elsas et al.

Summary: A small population of CD163(hi) tissue-resident macrophages is identified to be responsible for primary and secondary resistance against T-cell-based immunotherapies. While these CD163(hi) M2 macrophages are resistant to Csf1r-targeted therapies, in-depth characterization and identification of the underlying mechanisms driving immunotherapy resistance allows the specific targeting of this subset of macrophages, thereby creating new opportunities for therapeutic intervention with the aim to overcome immunotherapy resistance.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2023)

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Article Engineering, Biomedical

Cooperative phagocytosis of solid tumours by macrophages triggers durable anti-tumour responses

Lawrence J. Dooling et al.

Summary: By disrupting the CD47-SIRP alpha macrophage checkpoint and delivering a tumour-opsonizing monoclonal antibody, durable anti-tumour responses can be triggered by maximizing the cooperative phagocytic potency of macrophages.

NATURE BIOMEDICAL ENGINEERING (2023)

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Article Cardiac & Cardiovascular Systems

Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction

Alan J. Mouton et al.

Summary: Metabolic reprogramming from glycolysis to the mitochondrial TCA cycle and oxidative phosphorylation may mediate macrophage polarization from M1 to M2 phenotype after myocardial infarction. Changes in cardiac macrophage glucose metabolism reflect polarization status, mainly in monocyte-derived but not resident macrophages.

FRONTIERS IN CARDIOVASCULAR MEDICINE (2023)

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Review Immunology

Treg specialization and functions beyond immune suppression

Jillian L. Astarita et al.

Summary: Regulatory T cells (Tregs) not only suppress immune responses, but also have a diverse range of functions such as tissue repair, angiogenesis, basal metabolism, and stem cell maintenance. Tregs play a crucial role in maintaining the balance between immunity and tolerance, and their importance is highlighted by the development of autoimmunity in the absence or dysfunction of Tregs. In addition to their immunoregulatory roles, Tregs have been found to have non-immune modulatory functions, which are essential for regulating health and disease.

CLINICAL AND EXPERIMENTAL IMMUNOLOGY (2023)

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Article Oncology

Age-associated microenvironmental changes highlight the role of PDGF-C in ER+ breast cancer metastatic relapse

Frances K. Turrell et al.

Summary: Patients with estrogen receptor (ER)-positive breast cancer are at risk of metastatic relapse due to dormant disseminated tumor cells (DTCs) reawakening at secondary sites. Aging or fibrotic microenvironment promotes DTC proliferation and upregulates tumor cell Pdgfc expression, stimulating further stromal activation. This study suggests targeting PDGF-C signaling could limit metastatic relapse in ER+ breast cancer.

NATURE CANCER (2023)

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Article Cell Biology

OX40 agonism enhances PD-L1 checkpoint blockade by shifting the cytotoxic T cell differentiation spectrum

Tetje C. van der Sluis et al.

Summary: Immune checkpoint therapy (ICT) has the potential to eliminate cancer, but the underlying mechanisms determining its effectiveness are not fully understood. By using high-dimensional single-cell profiling, this study investigates if the T cell landscape in peripheral blood can predict responses to combinatorial targeting of the OX40 costimulatory and PD-1 inhibitory pathways. The findings reveal dynamic activation states of therapy-responsive T cells and emphasize the importance of NK cell receptors and chemokine receptors in therapy-induced anti-tumor immunity.

CELL REPORTS MEDICINE (2023)

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Review Endocrinology & Metabolism

The exercise IL-6 enigma in cancer

Samuel T. Orange et al.

Summary: IL-6 has both anticancer and procancer effects depending on the context, known as the 'exercise IL-6 enigma'. Exercise-induced IL-6 can protect against cancer by improving insulin sensitivity, stimulating the production of anti-inflammatory cytokines, mobilizing immune cells, and reducing DNA damage. However, IL-6 continuously produced in inflammatory sites drives tumorigenesis by promoting chronic inflammation. This review explores the roles of IL-6 in chronic inflammation, tumorigenesis, and exercise-associated cancer prevention and identifies the factors underlying the exercise IL-6 enigma.

TRENDS IN ENDOCRINOLOGY AND METABOLISM (2023)

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Correction Medicine, Research & Experimental

Epigenetics in glaucoma: a link between histone methylation and neurodegeneration (vol 132, e163670, 2022)

Wendy W. Liu et al.

JOURNAL OF CLINICAL INVESTIGATION (2023)

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Review Biochemistry & Molecular Biology

Angiogenic signaling pathways and anti-angiogenic therapy for cancer

Zhen-Ling Liu et al.

Summary: Angiogenesis is a complex process regulated by various molecules and plays a crucial role in tumor growth and metastasis. Targeted therapeutic research based on these molecules has led to the emergence of promising anti-angiogenic strategies in cancer therapy.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

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Article Oncology

PSGL-1 is a novel tumor microenvironment prognostic biomarker with cervical high-grade squamous lesions and more

Yingying Lin et al.

Summary: This study investigated the expression and clinical significance of PSGL-1 in cervical cancer. Results showed that PSGL-1 expression correlated with cervical lesion development and had a higher expression in HPV positive cases. The optimal cut-off value of PSGL-1 for predicting CIN2+ was 0.245. Higher PSGL-1 expression was associated with better prognosis and immune cell infiltration in cervical cancer.

FRONTIERS IN ONCOLOGY (2023)

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Article Medicine, Research & Experimental

Development and validation of an integrative pan-solid tumor predictor of PD-1/PD-L1 blockade benefit

Scott A. Tomlins et al.

Summary: A predictive model called Immunotherapy Response Score (IRS) was developed by combining tumor mutation burden (TMB) with CD274, PDCD1, ADAM12, and TOP2A expression to predict the efficacy of immune checkpoint inhibitors. In a validation study, patients with high IRS showed better progression-free survival (rwPFS) and overall survival (OS) compared to patients with low IRS. This study suggests that the IRS model can expand the application of PD-(L)1 monotherapy beyond currently approved indications.

COMMUNICATIONS MEDICINE (2023)

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Review Biochemistry & Molecular Biology

Emerging phagocytosis checkpoints in cancer immunotherapy

Yu'e Liu et al.

Summary: Cancer immunotherapy utilizes immune checkpoints-targeted therapy and adoptive transfer of engineered immune cells to mobilize patients' own immune systems against cancer cells, revolutionizing the field of oncology. Phagocytosis checkpoints, including CD47, CD24, MHC-I, PD-L1, STC-1, and GD2, play essential roles in suppressing immune responses and linking innate and adaptive immunity in cancer immunotherapy. Genetic ablation and blockade of these checkpoints have shown promising results in enhancing phagocytosis and reducing tumor size. CD47 is the most extensively studied phagocytosis checkpoint and has emerged as a promising target for cancer treatment. However, challenges such as anemia and thrombocytopenia due to CD47's ubiquitous expression on erythrocytes need to be addressed. This review discusses the mechanisms, functions, clinical progress, challenges, and potential solutions of phagocytosis checkpoints in cancer immunotherapy, aiming to facilitate combined immunotherapeutic strategies involving both innate and adaptive immune responses.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2023)

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Article Immunology

CIS controls the functional polarization of GM-CSF-derived macrophages

Shengbo Zhang et al.

Summary: The cytokine GM-CSF can differentiate monocytes into macrophages with opposing functions, proinflammatory M1-like and immunosuppressive M2-like. In this study, it was found that the protein CIS plays a critical role in the GM-CSF signaling pathway, and deficiency of CIS leads to the differentiation of monocytes into immunosuppressive M2-like macrophages, promoting allergic inflammation.

CELLULAR & MOLECULAR IMMUNOLOGY (2023)

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Article Immunology

Surfactant protein D inhibits lipid-laden foamy macrophages and lung inflammation in chronic obstructive pulmonary disease

Miao-Hsi Hsieh et al.

Summary: Increased levels of SP-D and FMs are found in oxidative stress conditions and/or COPD patients. Our study reveals the crucial roles of SP-D in airway inflammation and emphysematous changes, and shows that rfhSP-D can reverse these changes.

CELLULAR & MOLECULAR IMMUNOLOGY (2023)

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Review Cell Biology

Scavenger receptors in host defense: from functional aspects to mode of action

Qamar Taban et al.

Summary: Scavenger receptors are a diverse group of proteins that play a major role in innate immunity and homeostasis. They act as pattern recognition receptors and work together with other co-receptors to generate immune responses against various ligands. Their functions include adhesion, endocytosis, and phagocytosis, among others.

CELL COMMUNICATION AND SIGNALING (2022)

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Article Immunology

MEF2C promotes M1 macrophage polarization and Th1 responses

Xibao Zhao et al.

Summary: This study demonstrates the critical role of MEF2C in regulating macrophage polarization, with involvement in inflammation and host defense through promoting the expression of interleukin-12. MEF2C deficiency leads to increased susceptibility to certain infections and protection against certain intestinal diseases.

CELLULAR & MOLECULAR IMMUNOLOGY (2022)

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Article Allergy

Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma

Antonie Lechner et al.

Summary: This study reveals the existence of macrophage-trained immunity in allergic asthma, characterized by inflammatory transcriptional reprogramming and excessive mediator responses. Allergen-triggered inflammation drives a TNF-dependent innate memory, which may perpetuate and exacerbate chronic type 2 airway inflammation and thus represents a target for asthma therapy.

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY (2022)

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Letter Oncology

HLF regulates ferroptosis, development and chemoresistance of triple-negative breast cancer by activating tumor cell-macrophage crosstalk

Hengyu Li et al.

Summary: Tumor-associated macrophages (TAMs) promote the activation of hepatic leukemia factor (HLF) in triple-negative breast cancer (TNBC) cells through the secretion of transforming growth factor-beta1 (TGF-beta 1) and subsequently, HLF transactivates gamma-glutamyltransferase 1 (GGT1) to enhance ferroptosis resistance. This process drives TNBC cell proliferation, metastasis, and cisplatin resistance. Additionally, TNBC cells activate the JAK2/STAT3 axis to induce TGF-beta 1 secretion by TAMs, forming a feed-forward circuit. The combination of HLF and GGT1 values can improve the accuracy of TNBC patient prognosis.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Article Biochemistry & Molecular Biology

MMP-9 secreted by M2-type macrophages promotes Wilms' tumour metastasis through the PI3K/AKT pathway

Kaixuan Tian et al.

Summary: M2-type macrophages enhance proliferation and metastasis of Wilms' tumour by secreting MMP9, thereby increasing the invasive ability of the tumour.

MOLECULAR BIOLOGY REPORTS (2022)

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Review Immunology

The impact of the lung environment on macrophage development, activation and function: diversity in the face of adversity

Calum C. Bain et al.

Summary: The last decade has seen significant advances in the field of macrophage biology, particularly in our understanding of their heterogeneity, ontogeny, metabolism, and function in both health and disease. Future research should focus on further advancing core concepts and addressing key unanswered questions.

MUCOSAL IMMUNOLOGY (2022)

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Article Biochemistry & Molecular Biology

Tumor-associated macrophages promote PD-L1 expression in tumor cells by regulating PKM2 nuclear translocation in pancreatic ductal adenocarcinoma

Qing Xia et al.

Summary: This study found that TGF-beta 1 secreted by TAMs promotes the expression of PD-L1 in PDAC cells by inducing nuclear translocation of PKM2. The interaction between PKM2 and STAT1 enhanced by TGF-beta 1 stimulation facilitates the transactivation of PD-L1. Knockdown of PKM2 decreases PD-L1 expression, promotes NK cell activation, inhibits tumor growth, and when combined with PD-1/PD-L1 blockade, limits tumor growth.

ONCOGENE (2022)

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Article Oncology

Macrophage-Targeted Therapy Unlocks Antitumoral Cross-talk between IFNγ-Secreting Lymphocytes and IL12-Producing Dendritic Cells

Christina Pfirschke et al.

Summary: Macrophages are frequently found in tumors and are associated with poor patient survival. In this study, the researchers investigated the effects of a CSF1R inhibitor on the lung tumor immune microenvironment and found that it reshaped the landscape of CSF1R-expressing cells, leading to enhanced antitumor immune responses mediated by non-macrophage cells.

CANCER IMMUNOLOGY RESEARCH (2022)

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Article Chemistry, Multidisciplinary

Smad3 Promotes Cancer-Associated Fibroblasts Generation via Macrophage-Myofibroblast Transition

Philip Chiu-Tsun Tang et al.

Summary: This study identified a novel role of macrophage-myofibroblast transition (MMT) in cancer, showing that MMT cells can de novo generate cancer-promoting cancer-associated fibroblasts (CAFs). Through fate-mapping, RNA velocity, and pseudotime analysis, a subset of CAFs derived from macrophages was confirmed in the tumor microenvironment. Targeting Smad3, a key regulator in the MMT process, effectively blocked CAF formation and cancer progression in vivo, suggesting MMT as a potential therapeutic target for cancer immunotherapy.

ADVANCED SCIENCE (2022)

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Editorial Material Medicine, General & Internal

CAR-macrophage: An extensive immune enhancer to fight cancer

Shuhang Wang et al.

EBIOMEDICINE (2022)

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Article Oncology

Pan-Cancer Analysis Shows Enrichment of Macrophages, Overexpression of Checkpoint Molecules, Inhibitory Cytokines, and Immune Exhaustion Signatures in EMT-High Tumors

Jayesh Kumar Tiwari et al.

Summary: This article analyzes the pan-cancer TIME of EMT, showing that EMT-high tumors have a highly immunosuppressive TIME compared to EMT-low tumors. The distinctive features of EMT-high tumors include the enrichment of tumor-associated macrophages, overexpression of immune checkpoint molecules, upregulation of immune inhibitory cytokines TGFB1 and IL10, and enrichment of inflammatory and exhausted CD8+ T-cell signatures. This study suggests the importance of analyzing and targeting the TIME regulators for anticancer immunotherapy.

FRONTIERS IN ONCOLOGY (2022)

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Article Oncology

Tumor-associated macrophage derived IL-6 enriches cancer stem cell population and promotes breast tumor progression via Stat-3 pathway

N. N. Radharani et al.

Summary: Tumor-associated macrophages (TAMs) promote tumor progression by interacting with breast cancer cells, expressing various proteins, including cytokines that enrich cancer stem cells (CSCs). TAMs produce high levels of Interleukin-6 (IL-6) through p38-MAPK pathway upon interaction with breast cancer cells. TAM-derived IL-6 activates Signal transducer and activator of transcription 3 (STAT-3) pathway, promotes CSC enrichment and influences tumor growth in breast cancer.

CANCER CELL INTERNATIONAL (2022)

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Article Oncology

The expression of PD-1 ligand 1 on macrophages and its clinical impacts and mechanisms in lung adenocarcinoma

Yusuke Shinchi et al.

Summary: PD-1 and PD-L1 are target molecules for immunotherapy in non-small cell lung cancer. This study investigated the clinical significance of PD-L1 expression on macrophages in lung adenocarcinoma and found that high PD-L1 expression was correlated with EGFR mutation, lower cancer grade, and shorter overall survival. The mechanism of PD-L1 overexpression on macrophages was found to be induced by GM-CSF derived from cancer cells via STAT3 activation. Anti-GM-CSF therapy inhibited cancer development, but had no effect on PD-L1 expression on macrophages. PD-L1 overexpression on macrophages via the GM-CSF/STAT3 pathway was suggested to promote cancer progression in lung adenocarcinoma.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2022)

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Article Biochemistry & Molecular Biology

Tissue-resident FOLR2+ macrophages associate with CD8+ T cell infiltration in human breast cancer

Rodrigo Nalio Ramos et al.

Summary: This study identifies a specific population of FOLR2(+) tissue-resident macrophages in healthy mammary gland and breast cancer primary tumors, which interact with CD8(+) T cells and positively correlate with better patient survival.

CELL (2022)

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Correction Oncology

First-in-Class Anti-Immunoglobulin-like Transcript 4 Myeloid-Specific Antibody MK-4830 Abrogates a PD-1 Resistance Mechanism in Patients with Advanced Solid Tumors (vol 28, pg 57, 2022)

Lillian L. Siu et al.

CLINICAL CANCER RESEARCH (2022)

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Article Biochemistry & Molecular Biology

Nlrp3 inflammasome activation in macrophages suffices for inducing autoinflammation in mice

Ulrika C. Frising et al.

Summary: Macrophages play an important role in driving CAPS in mice, while neutrophils act independently in propagating autoinflammation.

EMBO REPORTS (2022)

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Article Chemistry, Multidisciplinary

Intratumoral delivery of IL-12 and IL-27 mRNA using lipid nanoparticles for cancer immunotherapy

Jin-Qing Liu et al.

Summary: Localized therapy that delivers immune stimulatory cytokines directly to tumors improves therapeutic efficacy without causing systemic toxicity.

JOURNAL OF CONTROLLED RELEASE (2022)

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Article Chemistry, Multidisciplinary

Homeostasis inside Single Activated Phagolysosomes: Quantitative and Selective Measurements of Submillisecond Dynamics of Reactive Oxygen and Nitrogen Species Production with a Nanoelectrochemical Sensor

Yu-Ting Qi et al.

Summary: Reactive oxygen and nitrogen species (ROS/RNS) generated by macrophages play critical roles in phagocytosis and immune homeostasis. Researchers have developed a novel nanowire electrode to quantitatively and individually monitor the four primary ROS/RNS. The study provides insights into the rapid generation and concentration variations of ROS/RNS during phagocytosis and reveals the important mechanism of enzyme regulation for immune responses and immunotherapies.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2022)

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Article Oncology

Tumor-associated macrophages of the M1/M2 phenotype are involved in the regulation of malignant biological behavior of breast cancer cells through the EMT pathway

Zhuo Chen et al.

Summary: The study reveals that M2-tumor associated macrophages (TAMs) are more abundant in TNBC and associated with poor prognosis. M2-TAMs promote invasion, migration, and proliferation of breast cancer cells, possibly through the mechanism of epithelial-mesenchymal transition.

MEDICAL ONCOLOGY (2022)

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Article Cell Biology

Cancer-cell-secreted extracellular vesicles suppress insulin secretion through miR-122 to impair systemic glucose homeostasis and contribute to tumour growth

Minghui Cao et al.

Summary: Breast cancer-derived extracellular vesicles suppress pancreatic insulin secretion, leading to dysregulated glucose homeostasis and enhanced tumor growth by targeting PKM in beta-cells.

NATURE CELL BIOLOGY (2022)

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Article Multidisciplinary Sciences

Cancer stem cell regulated phenotypic plasticity protects metastasized cancer cells from ferroptosis

Mingming Wu et al.

Summary: The study reveals the role of breast cancer stem cell (BCSC) secretome in regulating the stem cell population, tumor-initiating capacity, and metastasis. DKK1 is identified as a key factor secreted by BCSCs that promotes differentiation and metastatic outgrowth. DKK1 increases the expression of SLC7A11 to protect metastasizing cancer cells from ferroptosis. Combination therapy with a ferroptosis inducer and a DKK1 inhibitor shows synergistic effects in reducing metastasis.

NATURE COMMUNICATIONS (2022)

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Article Multidisciplinary Sciences

Macrophages disseminate pathogen associated molecular patterns through the direct extracellular release of the soluble content of their phagolysosomes

Catherine J. Greene et al.

Summary: The process of eructophagy allows macrophages to release partially digested material from phagolysosomes to the plasma membrane, enhancing inflammatory potential and activating neighboring cells. This discovery is crucial for understanding disease progression and the immune response mechanism.

NATURE COMMUNICATIONS (2022)

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Article Cell Biology

CD4+ T-cell-derived IL-10 promotes CNS inflammation in mice by sustaining effector T cell survival

Nir Yogev et al.

Summary: Interleukin (IL)-10 is a prototypical anti-inflammatory cytokine that plays a role in immune homeostasis. In CNS inflammation, T-cell-derived IL-10 can promote inflammation and enhance autoimmunity.

CELL REPORTS (2022)

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Article Oncology

Targeting the PSGL-1 Immune Checkpoint Promotes Immunity to PD-1-Resistant Melanoma

Julia M. DeRogatis et al.

Summary: Therapeutically targeting PSGL-1 can reinvigorate antitumor immunity by enhancing effector T-cell responses and reducing regulatory T cells, thus delaying tumor growth in a melanoma mouse model.

CANCER IMMUNOLOGY RESEARCH (2022)

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Review Immunology

Tumor-Associated Macrophages Regulate PD-1/PD-L1 Immunosuppression

Yunzhou Pu et al.

Summary: This review summarizes the roles and mechanisms of tumor-associated macrophages (TAMs) in the resistance of PD-1/PD-L1 inhibitors. Various therapies, including inhibition of TAM differentiation and re-education of TAM activation, are available to recover the anticancer efficacy of PD-1/PD-L1 inhibitors.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Immunology

Signaling Pathways That Mediate Alveolar Macrophage Activation by Surfactant Protein A and IL-4

Belen Garcia-Fojeda et al.

Summary: This study explores how SP-A enhances the effects of IL-4 on macrophage proliferation and effector functions through the activation of PI3K-dependent branched pathways. SP-A can amplify IL-4-mediated signaling, promote AM proliferation and alternative activation by activating the mTORC1 and GSK3 branches.

FRONTIERS IN IMMUNOLOGY (2022)

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Review Immunology

HLA-G and the MHC Cusp Theory

Bruna Miglioranza Scavuzzi et al.

Summary: Human leukocyte antigens (HLA) are important genetic risk factors in many diseases, but the mechanisms underlying their associations remain unclear. The MHC Cusp theory posits that in addition to antigen presentation, MHC codes for allele-specific molecules that can trigger MHC-associated diseases through interactions with receptors. Empirical evidence has supported this theory in several HLA-Class II-associated autoimmune diseases.

FRONTIERS IN IMMUNOLOGY (2022)

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Article Oncology

Immunosuppressive tumor-associated macrophages expressing interlukin-10 conferred poor prognosis and therapeutic vulnerability in patients with muscle-invasive bladder cancer

Yijia Xu et al.

Summary: High infiltration of IL-10(+)TAMs is associated with inferior prognosis and better response to chemotherapy in MIBC. IL-10(+)TAMs with suppressive features are associated with an immunoevasive tumor microenvironment characterized by exhausted CD8(+) T cells, immature NK cells, and increased immune checkpoint expression.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2022)

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Article Oncology

Targeting Immunosuppressive Tumor-Associated Macrophages Using Innate T Cells for Enhanced Antitumor Reactivity

Yan-Ruide Li et al.

Summary: This study evaluates the potential of innate T cells for antitumor therapy, targeting both tumor cells and immunosuppressive tumor-associated macrophages. Recent developments in innate immune cell CAR therapy have opened up new possibilities for overcoming challenges in traditional therapies, especially in the realm of tumor treatment and immunotherapy.

CANCERS (2022)

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Article Oncology

Clinical implications of EGFR-associated MAPK/ERK pathway in multiple primary lung cancer

Naixin Liang et al.

CLINICAL AND TRANSLATIONAL MEDICINE (2022)

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Article Biology

β-elemene regulates M1-M2 macrophage balance through the ERK/JNK/P38 MAPK signaling pathway

Yingyu Zhou et al.

Summary: Beta-elemene regulates the balance of proinflammatory cytokines in mouse white adipose tissue through MAPK signaling, affecting the imbalance of M1-M2 macrophages and inhibiting the phosphorylation of MAPK pathways. These results suggest that beta-elemene may be a potential therapeutic medicine for macrophage-mediated chronic diseases.

COMMUNICATIONS BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

Influence of tumor cell-derived TGF-β on macrophage phenotype and macrophage-mediated tumor cell invasion

Laura Andrea Gonzalez Maldonado et al.

Summary: In oral squamous cell carcinoma, macrophages in the tumor microenvironment play a significant role in prognosis and disease survival. This study focuses on the effects of tumor cell-secreted TGF-beta on macrophage phenotype and macrophage-facilitated tumor invasion. The results show that blocking the effects of TGF-beta can affect macrophage phenotype and impact tumor cell invasion and chemotaxis differently.

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY (2022)

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Article Biochemistry & Molecular Biology

DAMPs Released from Proinflammatory Macrophages Induce Inflammation in Cardiomyocytes via Activation of TLR4 and TNFR

Carolina Neu et al.

Summary: Cardiac dysfunction is a life-threatening complication in sepsis. Proinflammatory macrophages activate different cardiac receptors and induce cardiac inflammation and caspase-3/7 activation. Inhibition of TLR4 and TNFR reduces cardiac inflammation, while inhibition of TNFR prevents NF kappa B translocation into the nuclei of cardiomyocytes. Inhibition of TLR3 reduces macrophage-mediated caspase-3/7 activation.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2022)

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Article Multidisciplinary Sciences

Dendritic cells direct circadian anti-tumour immune responses

Chen Wang et al.

NATURE (2022)

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Article Multidisciplinary Sciences

Ras drives malignancy through stem cell crosstalk with the microenvironment

Shaopeng Yuan et al.

Summary: This study demonstrates that after activation of the oncogenic RAS gene, cancer stem cells in mice rewire their gene expression and engage in abnormal signaling crosstalk with their tissue microenvironment, driving malignant progression. These findings have important implications for cancer therapeutics.

NATURE (2022)

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Article Cell Biology

Alveolar macrophages instruct CD8+T cell expansion by antigen cross-presentation in lung

Takumi Kawasaki et al.

Summary: Alveolar macrophages function as antigen-presenting cells to support the expansion of lung CD8+ memory T cells and play a protective role during viral infection. This process relies on antigen cross-presentation and high expression of interleukin-18 by alveolar macrophages.

CELL REPORTS (2022)

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Article Multidisciplinary Sciences

LACC1 bridges NOS2 and polyamine metabolism in inflammatory macrophages

Zheng Wei et al.

Summary: The study reveals a previously unidentified pathway in inflammatory macrophages, elucidating the biochemical function of LACC1 in converting l-citrulline to l-ornithine and isocyanic acid. The findings suggest that l-ornithine could serve as a nutraceutical to ameliorate LACC1-associated immunological dysfunctions.

NATURE (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 Biotechnology & Applied Microbiology

Macrophages as tools and targets in cancer therapy

Alberto Mantovani et al.

Summary: This review discusses the molecular mechanisms of macrophage reprogramming in the tumor microenvironment and provides an overview of macrophage-targeted therapies for cancer treatment.

NATURE REVIEWS DRUG DISCOVERY (2022)

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Article Cell Biology

Effect of M2-like macrophages of the injured-kidney cortex on kidney cancer progression

Taisuke Ishii et al.

Summary: The presence of M2-like macrophages in the injured kidney promotes kidney cancer progression and resistance to anti-PD1 antibody through their pro-tumor function and inhibition of CD8(+) T cell infiltration. Macrophages positive for SLC7A11 are associated with poor prognosis in kidney cancer patients.

CELL DEATH DISCOVERY (2022)

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Review Biochemistry & Molecular Biology

Targeting tumor-associated macrophages for cancer treatment

Mengjun Li et al.

Summary: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment due to their immunosuppressive and other functions, making them important targets for anti-cancer strategies. However, the heterogeneity of TAMs makes the targeting strategy variable and uncertain. Identifying the subset specificity of TAMs may be a future option for treatment.

CELL AND BIOSCIENCE (2022)

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Article Oncology

Increased glucose metabolism in TAMs fuels O-GlcNAcylation of lysosomal Cathepsin B to promote cancer metastasis and chemoresistance

Qingzhu Shi et al.

Summary: Glucose metabolism plays a role in remodeling the functions of tumor-associated macrophages (TAMs) and promotes cancer metastasis and chemoresistance. This is achieved through the O-GlcNAcylation of Cathepsin B, which is mediated by lysosome-localized O-GlcNAc transferase (OGT) and leads to increased secretion of mature Cathepsin B in the tumor microenvironment.

CANCER CELL (2022)

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Article Immunology

Differential plasticity and fate of brain-resident and recruited macrophages during the onset and resolution of neuroinflammation

Karen De Vlaminck et al.

Summary: By examining the fate of microglia, border-associated macrophages (BAMs), and recruited macrophages during neuroinflammation and resolution, it was found that their responses and dynamics differ.

IMMUNITY (2022)

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Article Biochemistry & Molecular Biology

CircSMARCC1 facilitates tumor progression by disrupting the crosstalk between prostate cancer cells and tumor-associated macrophages via miR-1322/CCL20/CCR6 signaling

Tao Xie et al.

Summary: This study reveals that circSMARCC1 upregulates the secretion of chemokine CCL20 by sponging miR-1322, which mediates the interaction between tumor cells and TAMs, promoting the progression of PCa.

MOLECULAR CANCER (2022)

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Review Biochemistry & Molecular Biology

The hypoxia-driven crosstalk between tumor and tumor-associated macrophages: mechanisms and clinical treatment strategies

Ruixue Bai et al.

Summary: Hypoxia is considered a major target in cancer treatment, as it is a persistent feature in solid tumors and drives cancer malignancy. Tumor-associated macrophages (TAMs) heavily accumulate in hypoxic tumor regions and the interaction between TAMs and hypoxia contributes to increased tumor aggressiveness. Understanding the molecular mechanisms underlying the hypoxia-mediated communication between tumor cells and TAMs can provide insights for developing novel therapeutic strategies.

MOLECULAR CANCER (2022)

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Article Immunology

Differences in CD80 and CD86 transendocytosis reveal CD86 as a key target for CTLA-4 immune regulation

Alan Kennedy et al.

Summary: CD28 and CTLA-4 play important roles in regulating T cell immunity. The study found that CTLA-4 captures ligands through transendocytosis, and CD80 leads to ubiquitination and degradation of CTLA-4, while CD86 allows CTLA-4 to detach and recycle back to the cell surface. Clinically relevant mutations disrupt CD86 transendocytosis and are associated with autoimmune diseases.

NATURE IMMUNOLOGY (2022)

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Article Pharmacology & Pharmacy

Systematic pan-cancer analysis identifies APOC1 as an immunological biomarker which regulates macrophage polarization and promotes tumor metastasis

Liwen Ren et al.

Summary: APOC1 is closely associated with immune cell infiltration in multiple cancers and primarily expressed in macrophages. It is significantly co-expressed with immune cell infiltration, immune checkpoints, MHC molecules, chemokines, and other immune-related genes. Experimental results suggest that APOC1 regulates macrophage polarization and promotes tumor metastasis in renal cell cancer.

PHARMACOLOGICAL RESEARCH (2022)

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Article Multidisciplinary Sciences

Visualizing inflammation with an M1 macrophage selective probe via GLUT1 as the gating target

Heewon Cho et al.

Summary: This study presents a fluorescent probe named CDr17 that selectively targets M1 macrophages. The probe shows potential for tracking M1 macrophages in vivo and provides a valuable tool for studying macrophage activation and function. The development of subset-specific probes is crucial for understanding the diverse roles of macrophages.

NATURE COMMUNICATIONS (2022)

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Article Biology

HLJ1 amplifies endotoxin-induced sepsis severity by promoting IL-12 heterodimerization in macrophages

Wei-Jia Luo et al.

Summary: HLJ1 knockout mice show reduced organ injury and mortality in lipopolysaccharide-induced endotoxic shock. HLJ1 deletion affects IFN-gamma-related gene signatures in distinct immune cell clusters. HLJ1 deficiency leads to reduced IL-12 levels, dampened IFN-gamma production in natural killer cells, and improved survival rate. HLJ1 converts misfolded IL-12p35 homodimers to monomers, maintaining bioactive IL-12p70 heterodimerization and secretion.

ELIFE (2022)

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Article Biology

Macrophage innate training induced by IL-4 and IL-13 activation enhances OXPHOS driven anti-mycobacterial responses

Mimmi L. E. Lundahl et al.

Summary: This study provides new and unexpected insights into alternative macrophage activation states in the context of mycobacterial infection. Activation with IL-4 and IL-13 induces protective innate memory against mycobacterial challenge and enhances the killing capacity of macrophages. IL-4/13 trained macrophages retain heightened oxidative phosphorylation metabolism and impede heightened pro-inflammatory cytokine responses by inhibiting oxidative phosphorylation.

ELIFE (2022)

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Article Oncology

Metabolic remodeling in tumor-associated macrophages contributing to antitumor activity of cryptotanshinone by regulating TRAF6-ASK1 axis

Jia-Ha Yen et al.

Summary: The study reveals that cryptotanshinone (CPT) can convert TAMs from an M2 phenotype to an M1 phenotype, leading to tumor regression. CPT inhibits mitochondrial oxidative phosphorylation and fusion through autophagy and activates the ASK1 pathway. These findings provide a new macrophage-based approach for cancer immunotherapy.

MOLECULAR THERAPY-ONCOLYTICS (2022)

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Article Multidisciplinary Sciences

Single-cell RNA sequencing uncovers a neuron-like macrophage subset associated with cancer pain

Philip Chiu-Tsun Tang et al.

Summary: This study discovered a direct mechanism of tumor-associated macrophage (TAM) for promoting de novo neurogenesis, which contributes to a better understanding of tumor innervation. The study also identified a phenomenon of macrophage to neuron-like cell transition (MNT) and identified a crucial regulator for MNT. This finding has potential clinical significance for the treatment of cancer pain.

SCIENCE ADVANCES (2022)

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Article Engineering, Environmental

Superoxide Release by Macrophages through NADPH Oxidase Activation Dominating Chemistry by Isoprene Secondary Organic Aerosols and Quinones to Cause Oxidative Damage on Membranes

Ting Fang et al.

Summary: Secondary organic aerosols (SOA) can activate oxidases in macrophages to release superoxide, leading to oxidative stress. Among them, phenanthrenequinone (PQN) is more toxic. These findings provide a basis for further understanding of the adverse health effects and oxidative stress caused by fine particulate matter.

ENVIRONMENTAL SCIENCE & TECHNOLOGY (2022)

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Article Cell Biology

Periostin promotes ovarian cancer metastasis by enhancing M2 macrophages and cancer-associated fibroblasts via integrin-mediated NF-κB and TGF-β2 signaling

Sheng-Chieh Lin et al.

Summary: The study revealed that POSTN promotes tumor growth and metastasis by activating integrin/NF-kappa B signaling pathway, enhancing M2 macrophages and cancer-associated fibroblasts (CAF). This finding is of significance for the treatment of ovarian cancer.

JOURNAL OF BIOMEDICAL SCIENCE (2022)

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Article Rheumatology

Macrophage polarization toward M1 phenotype through NE-κB signaling in patients with Behcet's disease

Xiuhua Wu et al.

Summary: This study investigated the effect of BD serum on the phenotypes and functions of macrophage polarization. The findings revealed that BD serum promoted macrophage polarization towards a proinflammatory M1-like phenotype through NF-kappa B signaling. This may contribute to inflammation in BD. The study suggests that M1 polarized macrophages could be a potential therapeutic target for BD.

ARTHRITIS RESEARCH & THERAPY (2022)

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Article Immunology

Tumor-associated macrophage (TAM)-derived CCL22 induces FAK addiction in esophageal squamous cell carcinoma (ESCC)

Jie Chen et al.

Summary: This study reveals that tumor-associated macrophages produce CCL22, which promotes the malignant progression of cancer cells through the activation of the FAK/AKT pathway. The expression of CCL22 in the tumor stroma is positively correlated with tumor metastasis and reduced patient survival. The study also identifies DGK alpha as a signaling adaptor that links the CCL22 receptor CCR4 and FAK, and regulates the sensitivity of cancer cells to FAK inhibitors.

CELLULAR & MOLECULAR IMMUNOLOGY (2022)

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Review Biochemistry & Molecular Biology

LncRNA-Dependent Mechanisms of Transforming Growth Factor-β: From Tissue Fibrosis to Cancer Progression

Philip Chiu-Tsun Tang et al.

Summary: Transforming growth factor-beta (TGF-beta) plays a crucial role in inflammatory diseases by regulating immune cell activity and promoting extracellular matrix production. In cancer, TGF-beta enhances cancer cell invasion and metastasis by affecting stemness and epithelial mesenchymal transition. However, directly targeting TGF-beta could have undesirable outcomes as it also has protective anti-inflammatory and tumor-suppressive effects. Long non-coding RNAs (lncRNAs) associated with TGF-beta are being investigated as potential therapeutic targets for tissue fibrosis and cancer progression.

NON-CODING RNA (2022)

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Article Genetics & Heredity

Macrophage-mediated anti-tumor immunity against high-risk neuroblastoma

Xao X. Tang et al.

Summary: This study found that high-level expression of PD-L1 is associated with better prognosis in high-risk neuroblastoma patients, while patients with a PD-1/PD-L1 ratio >1 show inferior survival. High-level co-expression of SLAMF7 and SH2D1B is significantly associated with better survival in high-risk neuroblastoma patients.

GENES AND IMMUNITY (2022)

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Article Medicine, Research & Experimental

EZH2-triggered methylation of SMAD3 promotes its activation and tumor metastasis

Changsheng Huang et al.

Summary: This study reveals the critical role of EZH2-mediated SMAD3 K53/K333 methylation in the activation of SMAD3, which is associated with cancer metastasis and poor survival outcomes.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Medicine, Research & Experimental

ALK1 signaling is required for the homeostasis of Kupffer cells and prevention of bacterial infection

Dianyuan Zhao et al.

Summary: Tissue-derived signals regulate the identity and function of Kupffer cells through the BMP9/BMP10/ALK1 signaling pathway, while ALK1 is dispensable for the maintenance of macrophages.

JOURNAL OF CLINICAL INVESTIGATION (2022)

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Article Engineering, Biomedical

Breast cancer cells and macrophages in a paracrine-juxtacrine loop

Sevgi Onal et al.

Summary: The study found that macrophages exhibited chemotaxis towards BCC while BCC required direct contact to interact with macrophage-derived EGF. The interaction between breast cancer cells and macrophages is proposed to be a paracrine-juxtacrine loop involving CSF-1 and EGF, respectively.

BIOMATERIALS (2021)

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Review Immunology

Macrophages and the maintenance of homeostasis

David M. Mosser et al.

Summary: Macrophages should not only be considered immune cells, but more broadly as cellular transducers that interpret microenvironmental changes and actuate vital tissue responses. They sense a variety of inputs from their environment and transduce these inputs into different response outcomes to maintain homeostasis.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Review Immunology

Hepatic macrophages in liver homeostasis and diseases-diversity, plasticity and therapeutic opportunities

Yankai Wen et al.

Summary: Macrophages, key cellular components of the liver, play essential roles in maintaining liver homeostasis, injury and repair processes in liver diseases. Kupffer cells and monocyte-derived macrophages contribute significantly to tissue inflammation and injury, but exhibit different functional responses in distinct liver diseases.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Biotechnology & Applied Microbiology

DPP4/CD32b/NF-κB Circuit: A Novel Druggable Target for Inhibiting CRP-Driven Diabetic Nephropathy

Patrick Ming-Kuen Tang et al.

Summary: The study revealed that CRP plays a pathogenic role in diabetic nephropathy and DPP4 may serve as a potential therapeutic target. The use of linagliptin effectively blocks CRP-driven renal injury progression.

MOLECULAR THERAPY (2021)

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Article Oncology

The Prognostic Role of Macrophage Polarization in the Colorectal Cancer Microenvironment

Juha P. Vayrynen et al.

Summary: In colorectal cancer, high stromal density of M2-like macrophages is associated with worse cancer-specific survival, while stromal density of M1-like macrophages is not significantly linked to better survival. The ratio of M1 to M2 density in tumor stroma is associated with improved cancer-specific survival.

CANCER IMMUNOLOGY RESEARCH (2021)

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Article Oncology

Targeting MARCO and IL37R on Immunosuppressive Macrophages in Lung Cancer Blocks Regulatory T Cells and Supports Cytotoxic Lymphocyte Function

Linnea La Fleur et al.

Summary: The research revealed the correlation between MARCO-expressing TAMs and poor clinical outcomes in patients with non-small cell lung cancer. These TAMs block the antitumor activities of NK cells and T cells, and gain an immune-suppressive phenotype through the release of IL37. Targeting MARCO or IL37R may remodel the immune-suppressive microenvironment in lung cancer patients.

CANCER RESEARCH (2021)

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Article Cell Biology

M2 macrophages contribute to cell proliferation and migration of breast cancer

Daoyuan Tu et al.

Summary: Breast cancer is a malignant tumor that poses a serious threat to women's health, and research suggests that M2 macrophages, miR-1587, and IRF7 play crucial roles in cell proliferation, migration, and tumor growth in breast cancer. MiR-1587 targets the 3'UTR of IRF7 mRNA to regulate tumor progression.

CELL BIOLOGY INTERNATIONAL (2021)

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Article Engineering, Biomedical

M1 macrophage exosomes engineered to foster M1 polarization and target the IL-4 receptor inhibit tumor growth by reprogramming tumor-associated macrophages into M1-like macrophages

Gowri Rangaswamy Gunassekaran et al.

Summary: In this study, M1 macrophage-derived exosomes were engineered to reprogram TAMs into M1-like macrophages for inhibiting tumor growth. The results showed that systemic administration of these exosomes increased anti-tumor immunity more efficiently than untargeted and control peptide-labeled exosomes.

BIOMATERIALS (2021)

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Article Oncology

M2 macrophages secrete CXCL13 to promote renal cell carcinoma migration, invasion, and EMT

Yingwei Xie et al.

Summary: This study found that M2 macrophages in clear cell renal cell carcinoma are associated with poor prognosis, potentially promoting tumor proliferation, migration, and invasion through the secretion of chemokine CXCL13.

CANCER CELL INTERNATIONAL (2021)

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Article Immunology

Inflammatory M1-like macrophages polarized by NK-4 undergo enhanced phenotypic switching to an anti-inflammatory M2-like phenotype upon co-culture with apoptotic cells

Keizo Kohno et al.

Summary: The study demonstrates that NK-4 drives macrophage polarization towards an inflammatory M1-like phenotype and enhances phagocytic activity, playing a crucial role in resolving the inflammatory phase of wound healing.

JOURNAL OF INFLAMMATION-LONDON (2021)

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Article Immunology

Does tissue imprinting restrict macrophage plasticity?

Martin Guilliams et al.

Summary: Recent research has challenged the traditional view of macrophages as highly plastic cells, suggesting that the plasticity of resident macrophages may be limited by prolonged tissue residency. In contrast, recruited monocytes are more plastic and their differentiation process is influenced by both ongoing inflammation and the macrophage niche. This revised understanding of macrophage plasticity could provide new opportunities for resetting the macrophage pool after severe inflammatory events.

NATURE IMMUNOLOGY (2021)

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Article Oncology

Activity of tumor-associated macrophage depletion by CSF1R blockade is highly dependent on the tumor model and timing of treatment

Sarah A. O'Brien et al.

Summary: The study found that while anti-CSF1R treatment can reduce the number of tumor-associated macrophages (TAMs), it has minimal impact on the anti-tumor immune response in established tumors. In contrast, anti-CSF1R treatment concurrent with tumor implantation can better inhibit tumor growth and enhance anti-tumor immunity.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2021)

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Article Biochemistry & Molecular Biology

A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells

Sijin Cheng et al.

Summary: This study conducted a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, revealing distinct features of TIMs in different cancer types. For example, mast cells in nasopharyngeal cancer were associated with better prognosis, and pro-angiogenic TAMs showed diverse markers across different cancer types. The composition of TIMs appeared to be linked with certain features of somatic mutations and gene expressions.

CELL (2021)

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Article Multidisciplinary Sciences

CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours

Roberta Zappasodi et al.

Summary: By blocking CTLA-4, metabolic fitness and immune cell infiltration in tumours, especially those with low glycolytic activity, can be enhanced. This improves therapeutic outcomes, particularly in tumours with defective glycolysis, by destabilizing T-reg cells and promoting the activity of tumour-specific CD8(+) T cells.

NATURE (2021)

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Article Biochemistry & Molecular Biology

HDAC inhibition potentiates anti-tumor activity of macrophages and enhances anti-PD-L1-mediated tumor suppression

Xiaolei Li et al.

Summary: Pharmacological modulation of macrophage phenotype by HDAC inhibitors can reshape the tumor immune microenvironment, enhance anti-tumor immune responses, and improve the efficacy of immunotherapies in various tumors.

ONCOGENE (2021)

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Article Multidisciplinary Sciences

CAR-T cell-mediated depletion of immunosuppressive tumor-associated macrophages promotes endogenous antitumor immunity and augments adoptive immunotherapy

Alba Rodriguez-Garcia et al.

Summary: The study demonstrates that targeting FR beta-expressing TAMs with CAR-T cells can enhance antitumor immune responses and improve the efficacy of adoptive T-cell therapy in pre-clinical models.

NATURE COMMUNICATIONS (2021)

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Article Immunology

IL-10 Enhances Human Natural Killer Cell Effector Functions via Metabolic Reprogramming Regulated by mTORC1 Signaling

Zixi Wang et al.

Summary: The study demonstrates that IL-10 upregulates both glycolysis and oxidative phosphorylation in human NK cells, crucial for their enhanced effector functions. Mechanistically, it is revealed that IL-10 activates the mammalian target of rapamycin complex 1 (mTORC1) to regulate metabolic reprogramming in human NK cells.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Medicine, Research & Experimental

Macrophage-derived PDGF-B induces muscularization in murine and human pulmonary hypertension

Aglaia Ntokou et al.

Summary: The study reveals that macrophage-derived PDGF-B plays a critical role in pulmonary hypertension, and inhibition of lung macrophage PDGF-B using nanoparticles holds significant implications as an interventional strategy.

JCI INSIGHT (2021)

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Article Cell Biology

Targeting TREM2 on tumor-associated macrophages enhances immunotherapy

Mikhail Binnewies et al.

Summary: Research has identified a correlation between TREM2(+) tumor-associated macrophages (TAMs) and exhausted CD8(+) tumor-infiltrating lymphocytes (TILs), with therapy targeting TREM2 showing potential in promoting anti-tumor immunity.

CELL REPORTS (2021)

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Article Cell Biology

Global characterization of macrophage polarization mechanisms and identification of M2-type polarization inhibitors

Lizhi He et al.

Summary: Macrophages undergoing M1 versus M2-type polarization exhibit significant differences in cell metabolism, cellular functions, and signaling pathways, especially in metabolic pathways. Drug screens have identified inhibitors that selectively block M2-type polarization, with MEK signaling being found necessary for M2-type polarization in a proof-of-principle study using comprehensive proteomics and phosphoproteomics datasets.

CELL REPORTS (2021)

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Article Biochemistry & Molecular Biology

IL-8 secreted by tumor associated macrophages contribute to lapatinib resistance in HER2-positive locally advanced breast cancer via activation of Src/STAT3/ERK1/2-mediated EGFR signaling

Shaza Ahmed et al.

Summary: Locally advanced breast cancer (LABC) is a challenging disease with low survival rates due to treatment resistance, and the study suggests that the cytokine IL-8 secreted by TAMs may contribute to lapatinib resistance in LABC patients. Therefore, combination therapy to neutralize or block IL-8 action could potentially enhance the response to lapatinib treatment in LABC patients.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2021)

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Article Immunology

An Enriched Environment Alters DNA Repair and Inflammatory Responses After Radiation Exposure

Sae Sakama et al.

Summary: The study assessed the effects of enriched environment on radiation-induced carcinogenesis using a mouse model. The results showed that enrichment before radiation exposure improved responsiveness to DNA damage and immunity, further suppressing chronic inflammatory response, which may reduce the risk of radiation-induced carcinogenesis.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Gastroenterology & Hepatology

Genetic and Epigenetic Characteristics of Inflammatory Bowel Disease-Associated Colorectal Cancer

Kristiina Rajamaki et al.

Summary: By comprehensively characterizing IBD-associated tumorigenesis using multiple high-throughput approaches, distinct mechanisms of WNT pathway dysregulation were identified in IBD-CRC, which skew the tumors towards a mesenchymal subtype. Additionally, epigenetic modifications and noncoding mutations in specific genes were found in IBD-CRC, highlighting further differences compared to sCRC.

GASTROENTEROLOGY (2021)

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Article Oncology

USMB-shMincle: a virus-free gene therapy for blocking M1/M2 polarization of tumor-associated macrophages

Vivian Weiwen Xue et al.

Summary: The study demonstrates the development of a novel gene therapeutic approach targeting Mincle in a tumor-specific manner using the USMB system. The strategy effectively inhibits protumoral effects in mouse and human macrophages, showing potential for clinical translation in cancer treatment.

MOLECULAR THERAPY-ONCOLYTICS (2021)

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Review Oncology

Targeting Tumor-Associated Macrophages in Cancer Immunotherapy

Amy J. Petty et al.

Summary: Tumor-associated macrophages (TAMs) are the most abundant leukocyte population in most solid tumors and play a significant role in promoting tumor growth and metastasis. They are influenced by the tumor microenvironment and interact with other cell populations within the tumor milieu, leading to poor outcomes in multiple tumors. Therapeutic strategies targeting TAMs in cancer treatments focus on reducing monocyte recruitment, depleting or reprogramming TAMs, and targeting inhibitory molecules to enhance TAM-mediated phagocytosis.

CANCERS (2021)

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Article Immunology

LILRB4 suppresses immunity in solid tumors and is a potential target for immunotherapy

Naveen Sharma et al.

Summary: In this study, the inhibitory receptor LILRB4 was found on various intratumoral immune cell types in murine tumor models and human cancers, especially on TAMs. Inhibiting LILRB4 led to reduced tumor burden, increased survival, enhanced tumor immune infiltrates, and modulation of immune cell phenotypes. These findings suggest that LILRB4 strongly suppresses tumor immunity in the tumor microenvironment and blocking it could offer anti-tumor efficacy.

JOURNAL OF EXPERIMENTAL MEDICINE (2021)

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Article Immunology

CTLA4-Mediated Immunosuppression in Glioblastoma is Associated with the Infiltration of Macrophages in the Tumor Microenvironment

Xiudong Guan et al.

Summary: The study demonstrates that CTLA4 is positively correlated with the level and function of macrophages in the tumor microenvironment in glioblastoma, and has a certain impact on survival outcomes.

JOURNAL OF INFLAMMATION RESEARCH (2021)

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Article Cell Biology

Macrophages in SHH subgroup medulloblastoma display dynamic heterogeneity that varies with treatment modality

Mai T. Dang et al.

Summary: The study revealed significant changes in the composition of TAMs in medulloblastomas (MB) under different treatment modalities, with radiation inducing an immunosuppressive subset of TAMs. These findings highlight the important role of TAMs in tumor progression and response to therapy.

CELL REPORTS (2021)

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Article Genetics & Heredity

IFN-γ and TNF-α drive a CXCL10+CCL2+ macrophage phenotype expanded in severe COVID-19 lungs and inflammatory diseases with tissue inflammation

Fan Zhang et al.

Summary: Through single-cell transcriptomic analysis, shared immune cell states between COVID-19 and other inflammatory diseases were identified, providing insights for immunomodulatory therapies. A specific inflammatory macrophage phenotype was found in severe COVID-19 and other inflammatory diseases, induced by co-stimulation by IFN-gamma and TNF-alpha.

GENOME MEDICINE (2021)

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Article Oncology

IL-6 signaling in macrophages is required for immunotherapy-driven regression of tumors

Elham Beyranvand Nejad et al.

Summary: IL-6 signaling is critical for macrophage function under circumstances of immunotherapy-induced tumor tissue destruction, in line with the acute inflammatory functions of IL-6 signaling described in infections.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Review Oncology

New insights into M1/M2 macrophages: key modulators in cancer progression

Jiuyang Liu et al.

Summary: This article examines the critical roles of M1 and M2 macrophages in tumor progression, with M1 possessing anti-tumor properties and M2 promoting tumor growth and metastasis.

CANCER CELL INTERNATIONAL (2021)

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Review Cell Biology

Role of the CCL2-CCR2 signalling axis in cancer: Mechanisms and therapeutic targeting

Maosen Xu et al.

Summary: The chemokine ligand CCL2 and its receptor CCR2 play crucial roles in the initiation and progression of cancer by promoting tumor cell growth, migration, and recruitment of immunosuppressive cells. Studies have shown that therapeutic strategies targeting the CCL2-CCR2 axis are promising in combating cancer.

CELL PROLIFERATION (2021)

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Article Oncology

Allogeneic CAR Invariant Natural Killer T Cells Exert Potent Antitumor Effects through Host CD8 T-Cell Cross-Priming

Federico Simonetta et al.

Summary: The study assessed the antitumor effects of allogeneic CAR iNKT cells, demonstrating their ability to induce tumor-specific immunity across major MHC barriers and elicit potent antitumor responses from host CD8 T cells. This suggests that the use of off-the-shelf allogeneic CAR iNKT cells could address significant unmet needs in the clinic.

CLINICAL CANCER RESEARCH (2021)

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Article Oncology

Systemic Blockade of Clever-1 Elicits Lymphocyte Activation Alongside Checkpoint Molecule Downregulation in Patients with Solid Tumors: Results from a Phase I/II Clinical Trial

Reetta Virtakoivu et al.

Summary: The study revealed the unique role of the Clever-1 receptor in suppressing adaptive immune cells in the tumor microenvironment, suggesting that targeting this receptor may promote intratumoral proinflammatory responses and have potential therapeutic effects for patients with metastatic cancer.

CLINICAL CANCER RESEARCH (2021)

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Article Public, Environmental & Occupational Health

Systemic inflammation markers and cancer incidence in the UK Biobank

Therese Haugdahl Nost et al.

Summary: Systemic inflammation markers are associated with increased cancer risk and mortality. This study found associations between pre-diagnostic systemic inflammation markers and cancer risk, with SII showing the strongest impact on colorectal and lung cancer risk.

EUROPEAN JOURNAL OF EPIDEMIOLOGY (2021)

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Article Cell Biology

AANG: A natural compound formula for overcoming multidrug resistance via synergistic rebalancing the TGF-β/Smad signalling in hepatocellular carcinoma

Jeff Yat-Fai Chung et al.

Summary: The development of a natural compound formula AANG, derived from traditional Chinese medicine, has shown promising results in rebalancing TGF-beta/Smad signaling in the tumor microenvironment, thus inhibiting multidrug resistance in hepatocellular carcinoma patients.

JOURNAL OF CELLULAR AND MOLECULAR MEDICINE (2021)

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Review Gastroenterology & Hepatology

The multifaceted role of cathepsins in liver disease

Paloma Ruiz-Blazquez et al.

Summary: Proteases, as the most abundant enzyme gene family in vertebrates, play essential roles in maintaining important functions in living organisms. Lysosomal protease cathepsins, especially, play key roles in liver disease, participating in controlling processes such as apoptosis, extracellular matrix remodeling, and hepatocellular carcinoma.

JOURNAL OF HEPATOLOGY (2021)

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Article Medicine, Research & Experimental

HLA-dependent heterogeneity and macrophage immunoproteasome activation during lung COVID-19 disease

Christophe Desterke et al.

Summary: The study revealed a correlation between MHC class I antigen presentation in COVID-19 lung tissues and the amount of SARS-CoV-2 RNA, suggesting the activation of the immune system may be related to the level of viral antigen. Additionally, a higher number of stronger presenting alleles in Asian populations may explain the lower spread of the disease in this region.

JOURNAL OF TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

Macrophage depletion induces edema through release of matrix-degrading proteases and proteoglycan deposition

Stefan Bissinger et al.

Summary: In this study, it was found that edema formation in mice and cancer patients treated with CSF1R blockade was associated with body fluid retention, increased MMP activity, and elevated levels of HA and proteoglycans. Discontinuation of treatment or MMP inhibition could alleviate edema. Elevated levels of HA in peripheral blood may serve as a predictive marker for edema development in patients.

SCIENCE TRANSLATIONAL MEDICINE (2021)

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Article Cell Biology

Exosomal transfer of tumor-associated macrophage-derived hsa_circ_0001610 reduces radiosensitivity in endometrial cancer

Xiaobin Gu et al.

Summary: The study revealed that TAM-derived exosomes transfer hsa_circ_0001610 to EC cells, leading to a reduction in radiosensitivity by upregulating cyclin B1 expression through adsorbing miR-139-5p.

CELL DEATH & DISEASE (2021)

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Article Multidisciplinary Sciences

STING suppresses bone cancer pain via immune and neuronal modulation

Kaiyuan Wang et al.

Summary: STING agonists provide remarkable protection against cancer pain, bone destruction, and local tumor burden through direct neuronal modulation, modulation of immune cell function, and osteoclast function in the tumor microenvironment, offering long-term cancer pain relief.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Monocyte-derived and M1 macrophages from ankylosing spondylitis patients released higher TNF-α and expressed more IL1B in response to BzATP than macrophages from healthy subjects

Maryam Akhtari et al.

Summary: Macrophages play a role in the pathogenesis of ankylosing spondylitis by producing inflammatory cytokines in response to extracellular adenosine triphosphate (eATP). A study investigated the effect of BzATP on monocyte-generated and M1 macrophages from AS patients and controls, finding that AS macrophages were more sensitive and responded more intensively to BzATP. The diverse effects of BzATP on different types of macrophages suggest varied inflammatory properties in response to eATP.

SCIENTIFIC REPORTS (2021)

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Article Immunology

Arachidonic Acid Metabolism Controls Macrophage Alternative Activation Through Regulating Oxidative Phosphorylation in PPARγ Dependent Manner

Miao Xu et al.

Summary: Macrophage polarization is influenced by metabolic reprogramming in the tissue microenvironment, with arachidonic acid playing a key role in determining the phenotype of M2 macrophages. The metabolite PGE2 derived from arachidonic acid can either inhibit or facilitate M2 polarization of macrophages. PPAR gamma acts as a bridge between these processes by modulating oxidative phosphorylation.

FRONTIERS IN IMMUNOLOGY (2021)

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Article Oncology

Distinct Responsiveness of Tumor-Associated Macrophages to Immunotherapy of Tumors with Different Mechanisms of Major Histocompatibility Complex Class I Downregulation

Adrianna Piatakova et al.

Summary: Tumor-associated macrophages (TAMs) play a crucial role in the tumor microenvironment and their response to immunotherapy can vary depending on the expression of MHC-I molecules in the tumor. This study found that TAMs in tumors with distinct MHC-I expression levels show different immune reactions and cytotoxic capabilities. Consideration of these differences in TAMs is important for the development of effective cancer immunotherapies.

CANCERS (2021)

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Article Medicine, Research & Experimental

MMP2 and TLRs modulate immune responses in the tumor microenvironment

Luciana R. Muniz-Bongers et al.

Summary: The study revealed that MMP2 plays a promoting role in melanoma tumor growth by reducing cytolytic cells and increasing M2 macrophages. On the other hand, knockdown of MMP2 slows tumor growth and enhances T cell proliferation and NK cell recruitment. These effects of MMP2 are mediated through dysfunctional DC-T cell cross-talk.

JCI INSIGHT (2021)

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Article Oncology

Tumor-derived exosomal miR-19b-3p facilitates M2 macrophage polarization and exosomal LINC00273 secretion to promote lung adenocarcinoma metastasis via Hippo pathway

Jing Chen et al.

Summary: The research revealed that LUAD cells induced M2 polarization of TAMs by transporting miR-19b-3p via exosomes, activating STAT3 pathway to promote tumor metastasis. The interactive communication between LUAD cells and TAMs through exchange of exosomal miR-19b-3p and LINC00273 was elucidated, proving the pro-metastatic effect of this interchange. These findings offer a new perspective for developing LUAD treatment.

CLINICAL AND TRANSLATIONAL MEDICINE (2021)

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Article Oncology

The pan-cancer landscape of crosstalk between epithelial-mesenchymal transition and immune evasion relevant to prognosis and immunotherapy response

Guangyu Wang et al.

Summary: This study reveals the complex interplay between EMT and immune evasion, as well as their significant impact on tumor behavior and clinical outcomes. Quantitative analysis identified factors associated with the balance between EMT and immune evasion, such as cellular composition, mutation burden, chromosomal stability, and oncogenic gene alterations. The proposed EMT-CYT Index (ECI) scoring model emerged as a superior predictor of prognosis and immunotherapy response across different malignancies.

NPJ PRECISION ONCOLOGY (2021)

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Article Cell Biology

Development of allogeneic HSC-engineered iNKT cells for off-the-shelf cancer immunotherapy

Yan-Ruid Li et al.

Summary: Through hematopoietic stem cell gene engineering and in vitro differentiation, human allogeneic iNKT cells can be produced at high yield and purity, effectively targeting tumor cells with low immunogenicity. These cells can be further engineered to enhance tumor targeting or reduce immunogenicity for potential cancer therapy.

CELL REPORTS MEDICINE (2021)

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Article Oncology

TNF-α-producing macrophages determine subtype identity and prognosis via AP1 enhancer reprogramming in pancreatic cancer

Mengyu Tu et al.

Summary: Large-scale genomic profiling of pancreatic cancer has identified two distinct subtypes - 'classical' and 'basal-like' - within the stromal immune microenvironment, influencing differential prognosis. Basal-like neoplastic state is sustained through BRD4-mediated cJUN/AP1 expression, inducing CCL2 to recruit TNF-alpha-secreting macrophages, which in turn forces classical neoplastic cells into an aggressive state via lineage reprogramming. Integration of various data sources revealed JUNB/AP1 (classical) and cJUN/AP1 (basal-like) driven regulation of PDAC subtypes.

NATURE CANCER (2021)

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Review Biochemistry & Molecular Biology

CD47/SIRPα pathway mediates cancer immune escape and immunotherapy

Xiao Jia et al.

Summary: Immune evasion of cancer cells is mediated by the SIRPα-CD47 axis, but blocking the CD47-SIRPα interaction can enhance phagocytic clearance of cancer cells, activate immune responses, promote antigen presentation, and ultimately activate antitumor immune responses.

INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES (2021)

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Review Biochemistry & Molecular Biology

Pattern recognition receptors in health and diseases

Danyang Li et al.

Summary: Pattern recognition receptors (PRRs) are a class of receptors that can directly recognize specific molecular structures on pathogens, apoptotic host cells, and damaged senescent cells, bridging nonspecific immunity and specific immunity. Through the recognition and binding of ligands, PRRs can produce immunoprotective effects against infections and tumors. Research on PRRs and their ligands has greatly enhanced understanding of the signaling pathways involved, providing insights for the treatment of immune-related diseases and tumors.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Biochemistry & Molecular Biology

The key roles of cancer stem cell-derived extracellular vesicles

Chaoyue Su et al.

Summary: Cancer stem cells (CSCs)-derived extracellular vesicles (EVs) play a significant role in tumor progression, including promoting tumor resistance, metastasis, angiogenesis, as well as maintaining stemness phenotype and tumor immunosuppression microenvironment.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Biochemistry & Molecular Biology

Targeting cancer stem cells for reversing therapy resistance: mechanism, signaling, and prospective agents

He-Ming Zhou et al.

Summary: Understanding the key characteristics and resistance mechanisms of CSCs may improve patient outcomes and reduce relapse. Targeting the mechanisms and pathways of CSCs described in this review could lead to further drug discovery and therapy development.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Article Oncology

JMJD8 Promotes Malignant Progression of Lung Cancer by Maintaining EGFR Stability and EGFR/PI3K/AKT Pathway Activation

Bo Zhang et al.

Summary: JMJD8 functions as an oncogenic regulator in non-small-cell lung cancer (NSCLC), promoting carcinogenic activity by stabilizing EGFR and activating the downstream PI3K/AKT signaling pathway. High expression of JMJD8 is associated with the malignancy and staging of NSCLC patients.

JOURNAL OF CANCER (2021)

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Article Biochemistry & Molecular Biology

CSF1R inhibition depletes tumor-associated macrophages and attenuates tumor progression in a mouse sonic Hedgehog-Medulloblastoma model

I-Li Tan et al.

Summary: The immune microenvironment of tumors plays a critical role in tumor progression, with TAMs promoting SHH-MB progression in a mouse model. Inhibiting CSF1R reduces TAMs, prolongs survival, and decreases tumor volume, suggesting therapeutic potential for SHH-MB patients.

ONCOGENE (2021)

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Article Cardiac & Cardiovascular Systems

Interstitial macrophage-derived thrombospondin-1 contributes to hypoxia-induced pulmonary hypertension

Rahul Kumar et al.

CARDIOVASCULAR RESEARCH (2020)

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Review Biochemistry & Molecular Biology

Tumor angiogenesis: causes, consequences, challenges and opportunities

Roberta Lugano et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2020)

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Review Immunology

Biology and therapeutic potential of interleukin-10

Margarida Saraiva et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

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Article Cell Biology

Constitutively expressed MHC class Ib molecules regulate macrophage M2b polarization and sepsis severity in irradiated mice

Yunliang Yao et al.

JOURNAL OF LEUKOCYTE BIOLOGY (2020)

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Article Multidisciplinary Sciences

CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas

Joseph A. Flores-Toro et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Cell Biology

Mannose receptor (CD206) activation in tumor-associated macrophages enhances adaptive and innate antitumor immune responses

Jesse M. Jaynes et al.

SCIENCE TRANSLATIONAL MEDICINE (2020)

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Article Oncology

PD-L1 and PD-L2 expression in the tumor microenvironment including peritumoral tissue in primary central nervous system lymphoma

Motomasa Furuse et al.

BMC CANCER (2020)

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Review Oncology

Hypoxia: Turning vessels into vassals of cancer immunotolerance

Luana Schito et al.

CANCER LETTERS (2020)

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Article Oncology

Intratumoral Plasmid IL12 Electroporation Therapy in Patients with Advanced Melanoma Induces Systemic and Intratumoral T-cell Responses

Samantha K. Greaney et al.

CANCER IMMUNOLOGY RESEARCH (2020)

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Article Cell Biology

Knockdown of milk-fat globule EGF factor-8 suppresses glioma progression in GL261 glioma cells by repressing microglial M2 polarization

Wu Jing et al.

JOURNAL OF CELLULAR PHYSIOLOGY (2020)

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Article Cell Biology

Divergent Roles for Macrophage C-type Lectin Receptors, Dectin-1 and Mannose Receptors, in the Intestinal Inflammatory Response

Mouna Rahabi et al.

CELL REPORTS (2020)

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Article Multidisciplinary Sciences

A conserved dendritic-cell regulatory program limits antitumour immunity

Barbara Maier et al.

NATURE (2020)

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Article Cell Biology

M2 Macrophages Infiltrating Epithelial Ovarian Cancer Express MDR1: A Feature That May Account for the Poor Prognosis

Susann Badmann et al.

CELLS (2020)

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Article Biotechnology & Applied Microbiology

Human chimeric antigen receptor macrophages for cancer immunotherapy

Michael Klichinsky et al.

NATURE BIOTECHNOLOGY (2020)

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Article Oncology

Macrophage HIF-1α Is an Independent Prognostic Indicator in Kidney Cancer

Sophie J. Cowman et al.

CLINICAL CANCER RESEARCH (2020)

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Article Oncology

LncRNA FTX represses the progression of non-alcoholic fatty liver disease to hepatocellular carcinoma via regulating the M1/M2 polarization of Kupffer cells

Huajun Wu et al.

CANCER CELL INTERNATIONAL (2020)

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Article Biochemistry & Molecular Biology

Coupled scRNA-Seq and Intracellular Protein Activity Reveal an Immunosuppressive Role of TREM2 in Cancer

Yonatan Katzenelenbogen et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

TREM2 Modulation Remodels the Tumor Myeloid Landscape Enhancing Anti-PD-1 Immunotherapy

Martina Molgora et al.

CELL (2020)

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Article Immunology

Regulations of Glycolytic Activities on Macrophages Functions in Tumor and Infectious Inflammation

Qing Yu et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2020)

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Article Oncology

The Mincle/Syk/NF-κB Signaling Circuit Is Essential for Maintaining the Protumoral Activities of Tumor-Associated Macrophages

Chunjie Li et al.

CANCER IMMUNOLOGY RESEARCH (2020)

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Article Hematology

Thrombospondin-1 promotes haemostasis through modulation of cAMP signalling in blood platelets.

Ahmed Aburima et al.

BLOOD (2020)

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Article Multidisciplinary Sciences

Neural transcription factor Pou4f1 promotes renal fibrosis via macrophage-myofibroblast transition

Patrick Ming-Kuen Tang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Multidisciplinary Sciences

Basement membrane damage by ROS- and JNK-mediated Mmp2 activation drives macrophage recruitment to overgrown tissue

Neha Diwanji et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

STAT3 serine phosphorylation is required for TLR4 metabolic reprogramming and IL-1β expression

Jesse J. Balic et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

FGF2 alters macrophage polarization, tumour immunity and growth and can be targeted during radiotherapy

Jae Hong Im et al.

NATURE COMMUNICATIONS (2020)

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Article Oncology

Disabled Homolog 2 Controls Prometastatic Activity of Tumor- Associated Macrophages

Ilaria Marigo et al.

CANCER DISCOVERY (2020)

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Article Genetics & Heredity

Discovery of CD80 and CD86 as recent activation markers on regulatory T cells by protein-RNA single-cell analysis

Dominik Trzupek et al.

GENOME MEDICINE (2020)

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Article Medicine, Research & Experimental

Targeting tumor-associated macrophages and granulocytic myeloid-derived suppressor cells augments PD-1 blockade in cholangiocarcinoma

Emilien Loeuillard et al.

JOURNAL OF CLINICAL INVESTIGATION (2020)

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Review Oncology

Cancer stem cell secretome in the tumor microenvironment: a key point for an effective personalized cancer treatment

Julia Lopez de Andres et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Review Multidisciplinary Sciences

Concepts of extracellular matrix remodelling in tumour progression and metastasis

Juliane Winkler et al.

NATURE COMMUNICATIONS (2020)

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Article Immunology

Endometrial Cancer Cells Promote M2-Like Macrophage Polarization by Delivering Exosomal miRNA-21 under Hypoxia Condition

Li Xiao et al.

JOURNAL OF IMMUNOLOGY RESEARCH (2020)

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Article Oncology

CD47/SIRP alpha blocking peptide identification and synergistic effect with irradiation for cancer immunotherapy

Hongfei Wang et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Review Oncology

Therapy Resistance, Cancer Stem Cells and ECM in Cancer: The Matrix Reloaded

Kousik Kesh et al.

CANCERS (2020)

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Article Oncology

Tumor-derived exosomal miR-934 induces macrophage M2 polarization to promote liver metastasis of colorectal cancer

Senlin Zhao et al.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2020)

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Article Medicine, Research & Experimental

Tumor-associated macrophage, angiogenesis and lymphangiogenesis markers predict prognosis of non-small cell lung cancer patients

Ilseon Hwang et al.

JOURNAL OF TRANSLATIONAL MEDICINE (2020)

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Article Multidisciplinary Sciences

TLR signaling adapter BCAP regulates inflammatory to reparatory macrophage transition by promoting histone lactylation

Ricardo A. Irizarry-Caro et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Biology

Inhibition of the CCL2 receptor, CCR2, enhances tumor response to immune checkpoint therapy

Megan M. Tu et al.

COMMUNICATIONS BIOLOGY (2020)

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Article Neurosciences

Macrophage-Derived Vascular Endothelial Growth Factor-A Is Integral to Neuromuscular Junction Reinnervation after Nerve Injury

Chuieng-Yi Lu et al.

JOURNAL OF NEUROSCIENCE (2020)

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Article Oncology

Genetically engineered macrophages persist in solid tumors and locally deliver therapeutic proteins to activate immune responses

Katherine J. Brempelis et al.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2020)

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Article Oncology

Breast cancer cell debris diminishes therapeutic efficacy through heme oxygenase-1-mediated inactivation of M1-like tumor-associated macrophages

Seung Hyeon Kim et al.

NEOPLASIA (2020)

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Article Biotechnology & Applied Microbiology

Transcriptional regulatory networks of tumor-associated macrophages that drive malignancy in mesenchymal glioblastoma

Jason K. Sa et al.

GENOME BIOLOGY (2020)

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Review Biochemistry & Molecular Biology

The updated landscape of tumor microenvironment and drug repurposing

Ming-Zhu Jin et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Article Multidisciplinary Sciences

Tumor-initiating cells establish an IL-33-TGF-β niche signaling loop to promote cancer progression

Sachiko Taniguchi et al.

SCIENCE (2020)

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Article Medicine, Research & Experimental

IL-4 induces M2 macrophages to produce sustained analgesia via opioids

Melih O. Celik et al.

JCI INSIGHT (2020)

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Review Biochemistry & Molecular Biology

Targeting cancer stem cell pathways for cancer therapy

Liqun Yang et al.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2020)

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Article Engineering, Biomedical

Controlled M1-to-M2 transition of aged macrophages by calcium phosphate coatings

Jumana R. Alhamdi et al.

BIOMATERIALS (2019)

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Article Oncology

Tumor-Associated Macrophages Derived TGF-β-Induced Epithelial to Mesenchymal Transition in Colorectal Cancer Cells through Smad2,3-4/Snail Signaling Pathway

Jianhui Cai et al.

CANCER RESEARCH AND TREATMENT (2019)

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Article Oncology

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

Luca Cassetta et al.

CANCER CELL (2019)

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Article Oncology

Immunotherapeutic Blockade of Macrophage Clever-1 Reactivates the CD8+ T-cell Response against Immunosuppressive Tumors

Miro Viitala et al.

CLINICAL CANCER RESEARCH (2019)

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Article Medicine, Research & Experimental

Antigen delivery targeted to tumor-associated macrophages overcomes tumor immune resistance

Daisuke Muraoka et al.

JOURNAL OF CLINICAL INVESTIGATION (2019)

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Article Immunology

CCL22 controls immunity by promoting regulatory T cell communication with dendritic cells in lymph nodes

Moritz Rapp et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2019)

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Review Urology & Nephrology

Macrophages: versatile players in renal inflammation and fibrosis

Patrick Ming-Kuen Tang et al.

NATURE REVIEWS NEPHROLOGY (2019)

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Article Multidisciplinary Sciences

IL-10 produced by macrophages regulates epithelial integrity in the small intestine

Tina L. Morhardt et al.

SCIENTIFIC REPORTS (2019)

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Article Oncology

M2 macrophages mediate sorafenib resistance by secreting HGF in a feed-forward manner in hepatocellular carcinoma

Ningning Dong et al.

BRITISH JOURNAL OF CANCER (2019)

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Article Oncology

M2-like tumor-associated macrophages-secreted EGF promotes epithelial ovarian cancer metastasis via activating EGFR-ERK signaling and suppressing lncRNA LIMT expression

Xiang-Yang Zeng et al.

CANCER BIOLOGY & THERAPY (2019)

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Article Gastroenterology & Hepatology

HDAC6 Suppresses Let-7i-5p to Elicit TSP1/CD47-Mediated Anti-Tumorigenesis and Phagocytosis of Hepatocellular Carcinoma

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Macrophage CCL22 expression in the tumor microenvironment and implications for survival in patients with squamous cell carcinoma of the tongue

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Surfactant protein-D modulation of pulmonary macrophage phenotype is controlled by S-nitrosylation

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MMP-9 secreted by tumor associated macrophages promoted gastric cancer metastasis through a PI3K/AKT/Snail pathway

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Specific targeting of CD163+ TAMs mobilizes inflammatory monocytes and promotes T cell-mediated tumor regression

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Histone deacetylase inhibition promotes intratumoral CD8+ T-cell responses, sensitizing murine breast tumors to anti-PD1

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Immune cell PD-L1 co-localizes with macrophages and is associated with outcome in PD-1 pathway blockade therapy

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PD-L1 expression on tumor-infiltrating immune cells is highly associated with M2 TAM and aggressive malignant potential in patients with resected non-small cell lung cancer

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Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation

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CCL18 secreted from M2 macrophages promotes migration and invasion via the PI3K/Akt pathway in gallbladder cancer

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Human M2 Macrophages Limit NK Cell Effector Functions through Secretion of TGF-β and Engagement of CD85j

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mir-466a Targeting of TgF-β2 contributes to FoxP3+ regulatory T cell Differentiation in a Murine Model of allogeneic Transplantation

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TLR-3 Stimulation Skews M2 Macrophages to M1 Through IFN-αβ Signaling and Restricts Tumor Progression

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Macrophages sensing oxidized DAMPs reprogram their metabolism to support redox homeostasis and inflammation through a TLR2-Syk-ceramide dependent mechanism

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CD69 enhances immunosuppressive function of regulatory T-cells and attenuates colitis by prompting IL-10 production

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Gastric cancer mesenchymal stem cells derived IL-8 induces PD-L1 expression in gastric cancer cells via STAT3/mTOR-c-Myc signal axis

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Regulatory NLRs Control the RLR-Mediated Type I Interferon and Inflammatory Responses in Human Dendritic Cells

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Anti-CD47 Antibody As a Targeted Therapeutic Agent for Human Lung Cancer and Cancer Stem Cells

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Inhibition of CD47 Effectively Targets Pancreatic Cancer Stem Cells via Dual Mechanisms

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Priming of Human Resting NK Cells by Autologous M1 Macrophages via the Engagement of IL-1β, IFN-β, and IL-15 Pathways

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Stabilization of HIF-2α Induces sVEGFR-1 Production from Tumor-Associated Macrophages and Decreases Tumor Growth in a Murine Melanoma Model

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The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors

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Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species

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CXC chemokines: the regulatory link between inflammation and angiogenesis

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Human macrophage activation programs induced by bacterial pathogens

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