MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response

Article Gastroenterology & Hepatology

Identification of SCN7A as the key gene associated with tumor mutation burden in gastric cancer

Wenjie Li et al.

Summary: The tumor mutation burden (TMB) in gastric cancer (GC) is associated with prognosis. The hub gene SCN7A is identified as being associated with TMB, and its low expression is related to a better prognosis.

BMC GASTROENTEROLOGY (2022)

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Article Biotechnology & Applied Microbiology

Improved prediction of immune checkpoint blockade efficacy across multiple cancer types

Diego Chowell et al.

Summary: A machine learning model integrating genomic, molecular, demographic, and clinical data accurately predicts clinical response to immune checkpoint blockade in cancer patients. The model outperformed predictions based on tumor mutational burden and provides quantitative assessments of key model features. This approach is expected to substantially improve clinical decision-making in immunotherapy and inform future interventions.

NATURE BIOTECHNOLOGY (2022)

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Article Oncology

Anti-PD-L1/TGF-βR fusion protein (SHR-1701) overcomes disrupted lymphocyte recovery-induced resistance to PD-1/PD-L1 inhibitors in lung cancer

Bo Cheng et al.

Summary: Lung cancer patients with poor lymphocyte recovery may be resistant to anti-PD-1/PD-L1 antibodies but sensitive to second-generation agents such as SHR-1701.

CANCER COMMUNICATIONS (2022)

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Article Oncology

ITGB2 as a prognostic indicator and a predictive marker for immunotherapy in gliomas

Houshi Xu et al.

Summary: ITGB2 expression is significantly elevated in high-grade gliomas and predicts poor prognosis; high and low ITGB2 expression subgroups show different clinical outcomes and immune activation status; glioma patients with high ITGB2 expression levels have better response to immunotherapy.

CANCER IMMUNOLOGY IMMUNOTHERAPY (2022)

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Review Oncology

Cancer vaccines as promising immuno-therapeutics: platforms and current progress

Jian Liu et al.

Summary: Research on tumor immunotherapy has made significant progress, and cancer vaccines have emerged as a promising therapeutic strategy. Cancer vaccines stimulate anti-tumor immunity with tumor antigens, potentially overcoming immune suppression and inducing both humoral and cellular immunity. This review introduces the working mechanism of cancer vaccines, summarizes different development platforms, and highlights their clinical research progress, with a focus on clinical application and therapeutic efficacy.

JOURNAL OF HEMATOLOGY & ONCOLOGY (2022)

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Review Oncology

Antibody variable region engineering for improving cancer immunotherapy

Hantao Lou et al.

Summary: This review summarizes the application of antibody variable region engineering and discusses future directions for improving cancer therapies.

CANCER COMMUNICATIONS (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

PD-1 blockade-unresponsive human tumor-infiltrating CD8+ T cells are marked by loss of CD28 expression and rescued by IL-151

Kyung Hwan Kim et al.

Summary: This study investigated the role of CD28 in anti-PD-1 antibody-induced reinvigoration of human T cells and found that CD28 expression in human CD8(+)TILs is mainly expressed. Loss of CD28 expression serves as a marker of PD-1 blockade-unresponsive CD8(+) TILs in humans, highlighting potential mechanisms for combining IL-15 with anti-PD-1 antibodies.

CELLULAR & MOLECULAR IMMUNOLOGY (2021)

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Article Oncology

Dicer-independent snRNA/snoRNA-derived nuclear RNA 3 regulates tumor-associated macrophage function by epigenetically repressing inducible nitric oxide synthase transcription

Yang Shi et al.

Summary: This study identified a new class of nucleus-localized sRNAs, named snRNA/snoRNA-derived nuclear RNAs (sdnRNAs), with sdnRNA-3 selectively inhibiting transcription of Nos2 in macrophages by repressing chromatin accessibility at the Nos2 gene promoter. Higher expression of sdnRNA-3 was found in M2 TAMs in a B16 melanoma mouse model, and transfer of sdnRNA-3-silenced macrophages inhibited tumor growth.

CANCER COMMUNICATIONS (2021)

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Article Biochemistry & Molecular Biology

The circular RNA circDLG1 promotes gastric cancer progression and anti-PD-1 resistance through the regulation of CXCL12 by sponging miR-141-3p

Dong-Liang Chen et al.

Summary: The study highlights the upregulation of circDLG1 in distant metastatic lesions and gastric cancer tissues resistant to anti-PD-1 therapy, correlating with aggressive tumor phenotype and poor prognosis. Ectopic circDLG1 expression promotes proliferation, migration, invasion, and immune evasion of gastric cancer cells. Mechanistically, circDLG1 interacts with miR-141-3p as a miRNA sponge to increase CXCL12 expression, promoting gastric cancer progression and resistance to anti-PD-1 therapy.

MOLECULAR CANCER (2021)

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Article Oncology

Simultaneous Inhibition of LSD1 and TGFβ Enables Eradication of Poorly Immunogenic Tumors with Anti-PD-1 Treatment

Wanqiang Sheng et al.

Summary: Epigenetic regulators play a crucial role in cancer immunotherapy, with a combination of LSD1 inhibition, TGF beta, and PD-1 blockade being able to enhance CD8(+) T-cell infiltration and cytotoxicity, potentially targeting refractory tumors.

CANCER DISCOVERY (2021)

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Article Oncology

Response Rates to Anti-PD-1 Immunotherapy in Microsatellite-Stable Solid Tumors With 10 or More Mutations per Megabase

Cristina Valero et al.

Summary: This study confirmed higher response rates for tumors with TMB of 10 or more mutations per megabase following immune checkpoint inhibitor therapy across multiple cancer types. However, the predictive value of a universal numerical threshold for high TMB was limited, indicating a need for further investigation.

JAMA ONCOLOGY (2021)

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Article Cell Biology

IRF3-binding lncRNA-ISIR strengthens interferon production in viral infection and autoinflammation

Junfang Xu et al.

Summary: The lncRNA-ISIR directly binds to IRF3, promoting its activation and enhancing immune responses. In patients, the expression level of AK131315 is correlated with the severity of lupus. IFN-I-induced lncRNA-ISIR strengthens IRF3 activation by removing suppressive protein Fli-1.

CELL REPORTS (2021)

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Article Engineering, Biomedical

Elimination of acquired resistance to PD-1 blockade via the concurrent depletion of tumour cells and immunosuppressive cells

Gang Xue et al.

Summary: Targeting tumor cells can promote resistance to immune checkpoint blockade therapy, but this resistance can be overcome by depleting tumor cells and immunosuppressive cells simultaneously using a monoclonal antibody binding CD73 enzyme. This approach prevents tumors from acquiring resistance to immune checkpoint blockade and leads to the eradication of advanced tumors.

NATURE BIOMEDICAL ENGINEERING (2021)

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Article Multidisciplinary Sciences

Epigenetic silencing by SETDB1 suppresses tumour intrinsic immunogenicity

Gabriel K. Griffin et al.

Summary: A CRISPR-Cas9 screen in mouse tumour models treated with immune checkpoint blockade identified SETDB1 as an epigenetic checkpoint protein that suppresses tumour-intrinsic immunogenicity. Loss of SETDB1 leads to derepression of immune-stimulating genes and triggers TE-specific cytotoxic T cell responses, suggesting it as a potential target for immunotherapy in cancer treatment.

NATURE (2021)

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Article Genetics & Heredity

TGFβ1: An Indicator for Tumor Immune Microenvironment of Colon Cancer From a Comprehensive Analysis of TCGA

Jinyan Wang et al.

Summary: The immune component in TME is negatively related with CC stages. DEGs obtained from difference analysis are mainly enriched in immune-related activities. TGF beta 1 is significantly associated with gene communication in PPI network and the survival of CC patients, up-regulated in tumor samples, and related with poor prognosis of CC patients. Indicating TGF beta 1 as a potential indicator for CC tumor immune microenvironment and a prognostic factor, with potential for future immunotherapy.

FRONTIERS IN GENETICS (2021)

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Review Oncology

Treatment-related adverse events of PD-1 and PD-L1 inhibitor-based combination therapies in clinical trials: a systematic review and meta-analysis

Xiaoxiang Zhou et al.

Summary: This study comprehensively investigated the incidences and profiles of treatment-related adverse events in different PD-1 or PD-L1 inhibitor-based combination therapies. Results showed variations in the incidence and profiles of adverse events among different combination therapies, providing essential reference for clinicians in routine practice of cancer care.

LANCET ONCOLOGY (2021)

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Article Multidisciplinary Sciences

Structural basis of omega-3 fatty acid transport across the blood-brain barrier

Rosemary J. Cater et al.

Summary: This study presents the structure of MFSD2A, revealing how it mediates the uptake of lysolipids into the brain through Na+-dependent conformational changes. The transporter features an amphipathic cavity and a lateral gate, facilitating the release of substrates into the membrane.

NATURE (2021)

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Article Multidisciplinary Sciences

Notch signaling and efficacy of PD-1/PD-L1 blockade in relapsed small cell lung cancer

Nitin Roper et al.

Summary: This study identifies elevated Notch signaling as a significant predictor of clinical benefit in immune checkpoint blockade (ICB) for relapsed small cell lung cancer (SCLC) patients. Activation of Notch signaling induces a low NE phenotype, leading to increased expression of antigen processing and presentation machinery (APM) genes and improved intrinsic tumor immunity.

NATURE COMMUNICATIONS (2021)

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Article Oncology

Tumor microenvironment evaluation promotes precise checkpoint immunotherapy of advanced gastric cancer

Dongqiang Zeng et al.

Summary: This study established the predictive value of TMEscore in patients with mGC and identified associations between TMEscore and mutations, metabolic pathways, and epigenetic features through multi-omics data analysis. These findings suggest that exploration of TME in gastric cancer data could be beneficial for precision immunotherapy.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Review Oncology

Adoptive cellular therapy in solid tumor malignancies: review of the literature and challenges ahead

Kedar Kirtane et al.

Summary: Immune checkpoint inhibitors have significantly changed the standard care for many solid tumor malignancies, but resistance remains common. Adoptive cellular therapy is a rapidly growing form of immunotherapy that shows promise in overcoming resistance mechanisms and has already revolutionized the treatment of hematologic malignancies. The use of ACT in solid tumor malignancies is still in its early stages, with promising therapies under active investigation.

JOURNAL FOR IMMUNOTHERAPY OF CANCER (2021)

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Article Oncology

EZH2 inhibition activates a dsRNA-STING-interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer

Katherine L. Morel et al.

Summary: Combination of EZH2 inhibition and anti-PD-1 has been shown to enhance antitumor immune responses in prostate cancer by activating the dsRNA-STING-ISG stress response signaling; EZH2 inhibition upregulates genes involved in antigen presentation and interferon response, suggesting it as a therapeutic direction to enhance prostate cancer response to PD-1 CPI.

NATURE CANCER (2021)

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Article Biochemistry & Molecular Biology

TRIM41 is required to innate antiviral response by polyubiquitinating BCL10 and recruiting NEMO

Zhou Yu et al.

Summary: TRIM41 plays a crucial role in innate antiviral response by facilitating pathogenic nucleic acids-triggered signaling pathway, interacting with BCL10 and modifying its polyubiquitylation to activate NF-kappa B and TBK1-IRF3 pathways. The deficiency of TRIM41 leads to impaired immune response against viruses, suggesting its potential as a universal E3 ubiquitin ligase in innate antiviral defense mechanism.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

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Review Pharmacology & Pharmacy

TGF-beta: a master immune regulator

Christopher Larson et al.

EXPERT OPINION ON THERAPEUTIC TARGETS (2020)

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Article Immunology

Andrographolide potentiates PD-1 blockade immunotherapy by inhibiting COX2-mediated PGE2 release

Wen Liu et al.

INTERNATIONAL IMMUNOPHARMACOLOGY (2020)

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Article Oncology

Tumor Mutational Burden Determined by Panel Sequencing Predicts Survival After Immunotherapy in Patients With Advanced Gastric Cancer

Jinchul Kim et al.

FRONTIERS IN ONCOLOGY (2020)

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Review Oncology

Cancer Cell Metabolism Bolsters Immunotherapy Resistance by Promoting an Immunosuppressive Tumor Microenvironment

Zhou Jiang et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Multidisciplinary Sciences

Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer

Gregoire de Streel et al.

NATURE COMMUNICATIONS (2020)

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Letter Oncology

MUC4, MUC16, and TTN genes mutation correlated with prognosis, and predicted tumor mutation burden and immunotherapy efficacy in gastric cancer and pan-cancer

Yue Yang et al.

CLINICAL AND TRANSLATIONAL MEDICINE (2020)

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Article Immunology

Decreased Expression of the Host Long-Noncoding RNA-GM Facilitates Viral Escape by Inhibiting the Kinase activity TBK1 via S-glutathionylation

Yujia Wang et al.

IMMUNITY (2020)

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Review Oncology

Characteristics of the Tumor Microenvironment That Influence Immune Cell Functions: Hypoxia, Oxidative Stress, Metabolic Alterations

Ryan C. Augustin et al.

CANCERS (2020)

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Review Oncology

Sintilimab: A Promising Anti-Tumor PD-1 Antibody

Lin Zhang et al.

FRONTIERS IN ONCOLOGY (2020)

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Article Immunology

Low-dose decitabine enhances the effect of PD-1 blockade in colorectal cancer with microsatellite stability by re-modulating the tumor microenvironment

Ganjun Yu et al.

CELLULAR & MOLECULAR IMMUNOLOGY (2019)

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Article Gastroenterology & Hepatology

Human gastric cancer modelling using organoids

Therese Seidlitz et al.

GUT (2019)

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Article Immunology

The Lysophosphatidylcholine Transporter MFSD2A Is Essential for CD8+ Memory T Cell Maintenance and Secondary Response to Infection

Ann R. Piccirillo et al.

JOURNAL OF IMMUNOLOGY (2019)

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Article Oncology

Safety, efficacy and tumor mutational burden as a biomarker of overall survival benefit in chemo-refractory gastric cancer treated with toripalimab, a PD-1 antibody in phase Ib/II clinical trial NCT02915432

F. Wang et al.

ANNALS OF ONCOLOGY (2019)

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Review Oncology

The Tumor Microenvironment Innately Modulates Cancer Progression

Dominique C. Hinshaw et al.

CANCER RESEARCH (2019)

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Review Biochemistry & Molecular Biology

Long non-coding RNA PVT1 interacts with MYC and its downstream molecules to synergistically promote tumorigenesis

Ke Jin et al.

CELLULAR AND MOLECULAR LIFE SCIENCES (2019)

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Article Immunology

High Glucose Intake Exacerbates Autoimmunity through Reactive-Oxygen-Species-Mediated TGF-β Cytokine Activation

Dunfang Zhang et al.

IMMUNITY (2019)

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Article Oncology

Axitinib in Combination With Toripalimab, a Humanized Immunoglobulin G4 Monoclonal Antibody Against Programmed Cell Death-1, in Patients With Metastatic Mucosal Melanoma: An Open-Label Phase IB Trial

Xinan Sheng et al.

JOURNAL OF CLINICAL ONCOLOGY (2019)

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Review Oncology

Immune checkpoint inhibitors for the treatment of MSI-H/MMR-D colorectal cancer and a perspective on resistance mechanisms

Ibrahim Halil Sahin et al.

BRITISH JOURNAL OF CANCER (2019)

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Tumor-educated B cells selectively promote breast cancer lymph node metastasis by HSPA4-targeting IgG

Yan Gu et al.

NATURE MEDICINE (2019)

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Letter Pathology

MMR protein immunohistochemistry and microsatellite instability in gastric cancers

Junhun Cho et al.

PATHOLOGY (2019)

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Predicting tumour response to anti-PD-1 immunotherapy with computational modelling

Damijan Valentinuzzi et al.

PHYSICS IN MEDICINE AND BIOLOGY (2019)

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Tumor cell oxidative metabolism as a barrier to PD-1 blockade immunotherapy in melanoma

Yana G. Najjar et al.

JCI INSIGHT (2019)

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PD-1 Blockade Cellular Vesicles for Cancer Immunotherapy

Xudong Zhang et al.

ADVANCED MATERIALS (2018)

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Increased vessel perfusion predicts the efficacy of immune checkpoint blockade

Xichen Zheng et al.

JOURNAL OF CLINICAL INVESTIGATION (2018)

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Metastatic Brain Tumors Disrupt the Blood-Brain Barrier and Alter Lipid Metabolism by Inhibiting Expression of the Endothelial Cell Fatty Acid Transporter Mfsd2a

Shweta Tiwary et al.

SCIENTIFIC REPORTS (2018)

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Prostaglandin E2 Antagonizes TGF-β Actions During the Differentiation of Monocytes Into Dendritic Cells

Federico Remes Lenicov et al.

FRONTIERS IN IMMUNOLOGY (2018)

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Safety and Efficacy of Pembrolizumab Monotherapy in Patients With Previously Treated Advanced Gastric and Gastroesophageal Junction Cancer Phase 2 Clinical KEYNOTE-059 Trial

Charles S. Fuchs et al.

JAMA ONCOLOGY (2018)

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Identification of genomic alterations in nasopharyngeal carcinoma and nasopharyngeal carcinoma-derived Epstein-Barr virus by whole-genome sequencing

Chaofeng Tu et al.

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Efficacy of PD-1 or PD-L1 inhibitors and PD-L1 expression status in cancer: meta-analysis

Xian Shen et al.

BMJ-BRITISH MEDICAL JOURNAL (2018)

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Loss of PTEN Is Associated with Resistance to Anti-PD-1 Checkpoint Blockade Therapy in Metastatic Uterine Leiomyosarcoma

Suzanne George et al.

IMMUNITY (2017)

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Article Medicine, General & Internal

Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial

Yoon-Koo Kang et al.

LANCET (2017)

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Nivolumab in patients with metastatic DNA mismatch repair-deficient or microsatellite instability-high colorectal cancer (CheckMate 142): an open-label, multicentre, phase 2 study

Michael J. Overman et al.

LANCET ONCOLOGY (2017)

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Article Oncology

CD155T/TIGIT Signaling Regulates CD8+ T-cell Metabolism and Promotes Tumor Progression in Human Gastric Cancer

Weiling He et al.

CANCER RESEARCH (2017)

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Review Oncology

Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer

Clemence Granier et al.

ESMO OPEN (2017)

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Immunosuppressive cells in tumor immune escape and metastasis

Yang Liu et al.

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Characteristics and Significance of the Pre-metastatic Niche

Yang Liu et al.

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Tumor Exosomal RNAs Promote Lung Pre-metastatic Niche Formation by Activating Alveolar Epithelial TLR3 to Recruit Neutrophils

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CANCER CELL (2016)

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Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer

Martin Reck et al.

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Review Medicine, General & Internal

Dysregulation of TGFβ1 Activity in Cancer and Its Influence on the Quality of Anti-Tumor Immunity

Kristian M. Hargadon

JOURNAL OF CLINICAL MEDICINE (2016)

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Review Oncology

PD-L1 Expression as a Predictive Biomarker in Cancer Immunotherapy

Sandip Pravin Patel et al.

MOLECULAR CANCER THERAPEUTICS (2015)

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Prostaglandin E2 and programmed cell death 1 signaling coordinately impair CTL function and survival during chronic viral infection

Jonathan H. Chen et al.

NATURE MEDICINE (2015)

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Article Medicine, General & Internal

PD-1 Blockade in Tumors with Mismatch-Repair Deficiency

D. T. Le et al.

NEW ENGLAND JOURNAL OF MEDICINE (2015)

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Hepatic RIG-I Predicts Survival and Interferon-α Therapeutic Response in Hepatocellular Carcinoma

Jin Hou et al.

CANCER CELL (2014)

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Frequencies of circulating MDSC correlate with clinical outcome of melanoma patients treated with ipilimumab

Christiane Meyer et al.

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Mfsd2a is critical for the formation and function of the blood-brain barrier

Ayal Ben-Zvi et al.

NATURE (2014)

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TGF-β Effects on Prostate Cancer Cell Migration and Invasion Are Mediated by PGE2 through Activation of PI3K/AKT/mTOR Pathway

BaoHan T. Vo et al.

ENDOCRINOLOGY (2013)

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Major Facilitator Superfamily Domain-Containing Protein 2a (MFSD2A) Has Roles in Body Growth, Motor Function, and Lipid Metabolism

Justin H. Berger et al.

PLOS ONE (2012)

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MFSD2A is a novel lung tumor suppressor gene modulating cell cycle and matrix attachment

Monica Spinola et al.

MOLECULAR CANCER (2010)

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A novel phosphorylated STAT3 inhibitor enhances T cell cytotoxicity against melanoma through inhibition of regulatory T cells

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CANCER IMMUNOLOGY IMMUNOTHERAPY (2009)

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MFSD2A potentiates gastric cancer response to anti-PD-1 immunotherapy by reprogramming the tumor microenvironment to activate T cell response

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