ArticleCancer cell2023
CMTM6 shapes antitumor T cell response through modulating protein expression of CD58 and PD-L1.
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Article in Cancer cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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29citing papers in PubMed
9.7field-weighted citation impact, top 2% of its field
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- CMTM6 maintains B cell-intrinsic membrane CD40 stability to regulate anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- Regulation of natural killer cell infiltration and tumor progression by CMTM6 in gastric cancer.BMC cancer · 2026Article
- CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans.EMBO reports · 2026Article
- A federated digital twin reveals cytomegalovirus reactivation impairs CAR-T cell therapy via IL-15-mediated cytokine competition in B-Cell lymphoma.Frontiers in immunology · 2026Article
- TSIX: A Novel Long Noncoding RNA in Cancer Development and Progression.Current pharmaceutical design · 2026Review
- MAVS/CMTM6 axis couples mitochondrial homeostasis to immunogenic senescence via CCL3-driven T-cell recruitment in renal carcinoma.Journal for immunotherapy of cancer · 2025Article
- CD2 costimulation strength: A key regulator of T cell function and anti-tumor immunity that is epigenetically regulated.iScience · 2025Article
- Proteostasis of immune checkpoint receptors.The Biochemical journal · 2025Review
- Article
- Pancreatic cancer cells escape T/NK cell immune surveillance through the expressional separation of CD58.Journal for immunotherapy of cancer · 2025Article
- Inhibiting CMTM4 reverses the immunosuppressive function of myeloid-derived suppressor cells and augments immunotherapy response in cervical cancer.Journal for immunotherapy of cancer · 2025Article
- CMTM7 inhibits TLR4 signaling pathway via promoting Rab5 activation and alleviates acute liver injury.Cellular and molecular life sciences : CMLS · 2025Article
- Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment.Nature communications · 2025Article
- CMTM4 promotes the motility of colon cancer cells under radiation and is associated with an unfavorable neoadjuvant chemoradiotherapy response and patient survival in rectal cancer.Oncology letters · 2025Article
- Article
- CD58 reshapes the immunosuppressive microenvironment in gliomas through PD-L1 upregulation.Frontiers in oncology · 2025Article
- Comprehensive analysis of CMTM family and immune infiltration in esophageal carcinoma.PloS one · 2025Article
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Authors and funding
40 authors at 10 institutions in 5 countries.
Beiping MiaoGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Zhaoqing HuGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Riccardo MezzadraDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Lotte HoeijmakersDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Astrid FausterDivision of Biochemistry, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Shangce DuGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Medicine, Heidelberg University, 69120 Heidelberg, Germany.
Zhi YangDepartment of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Melanie Sator-SchmittGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Helena EngelGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Xueshen LiDepartment of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
Caroline BroderickDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Guangzhi JinDepartment of Interventional Radiology, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, No. 1111, Xianxia Road, Shanghai 200336, China.
Raquel Gomez-EerlandDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Lisette RozemanDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Xin LeiDepartment of Immunology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Hitoshi MatsuoGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Chen YangGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ingrid HoflandCore Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Dennis PetersCore Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Annegien BroeksCore Facility Molecular Pathology & Biobanking, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Elke LaportGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Annika FitzGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Xiyue ZhaoGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Mohamed A A MahmoudGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany; Faculty of Biosciences, Heidelberg University, 69120 Heidelberg, Germany.
Xiujian MaFaculty of Medicine, Heidelberg University, 69120 Heidelberg, Germany; German Cancer Research Center (DKFZ) Heidelberg, Division Molecular Neurogenetics, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Sandrine SanderGerman Cancer Research Center (DKFZ) Heidelberg, Division Adaptive Immunity and Lymphoma , Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Hai-Kun LiuGerman Cancer Research Center (DKFZ) Heidelberg, Division Molecular Neurogenetics, DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Guoliang CuiGerman Cancer Research Center (DKFZ) Heidelberg, Division T Cell Metabolism, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Yu GanDepartment of Biomedical Engineering, Stevens Institute of Technology, Hoboken, NJ 07030, USA.
Wei WuBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, the Netherlands; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A(∗)STAR), Singapore 138648, Singapore; Department of Pharmacy, National University of Singapore, Singapore 117543, Singapore.
Yanling XiaoDepartment of Immunology, Leiden University Medical Center (LUMC), Leiden, the Netherlands.
Albert J R HeckBiomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Padualaan 8, 3584 CH Utrecht, the Netherlands; Netherlands Proteomics Centre, Padualaan 8, 3584 CH Utrecht, the Netherlands.
Wenxian GuanDepartment of Gastrointestinal Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, China.
Scott W LoweDepartment of Cancer Biology and Genetics, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Hugo M HorlingsDepartment of Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Cun WangState Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Thijn R BrummelkampDivision of Biochemistry, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Christian U BlankDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Medical Oncology, Netherlands Cancer Institute (NKI), Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Medical Oncology, Leiden University Medical Centre (LUMC), Leiden, The Netherlands. Electronic address: c.blank@nki.nl.
Ton N M SchumacherDivision of Molecular Oncology & Immunology, Netherlands Cancer Institute, Oncode Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands; Department of Hematology, Leiden University Medical Center (LUMC), Leiden, the Netherlands. Electronic address: t.schumacher@nki.nl.
Chong SunGerman Cancer Research Center (DKFZ) Heidelberg, Division Immune Regulation in Cancer, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. Electronic address: c.sun@dkfz.de.
German Cancer Research Center · DEThe Netherlands Cancer Institute · NLMemorial Sloan Kettering Cancer Center · USShanghai Jiao Tong University · CNLeiden University Medical Center · NLOncode Institute · NLStevens Institute of Technology · USClinical Nutrition Research Centre · SGNanjing Drum Tower Hospital · CNUtrecht University · NL
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Hongbiao Carl Lekaye · 1985 to 2026
$347.4MNCI NIH HHS P30 CA008748
Abstract
The dysregulated expression of immune checkpoint molecules enables cancer cells to evade immune destruction. While blockade of inhibitory immune checkpoints like PD-L1 forms the basis of current cancer immunotherapies, a deficiency in costimulatory signals can render these therapies futile. CD58, a costimulatory ligand, plays a crucial role in antitumor immune responses, but the mechanisms controlling its expression remain unclear. Using two systematic approaches, we reveal that CMTM6 positively regulates CD58 expression. Notably, CMTM6 interacts with both CD58 and PD-L1, maintaining the expression of these two immune checkpoint ligands with opposing functions. Functionally, the presence of CMTM6 and CD58 on tumor cells significantly affects T cell-tumor interactions and response to PD-L1-PD-1 blockade. Collectively, these findings provide fundamental insights into CD58 regulation, uncover a shared regulator of stimulatory and inhibitory immune checkpoints, and highlight the importance of tumor-intrinsic CMTM6 and CD58 expression in antitumor immune responses.
Indexed as
B7-H1 AntigenMARVEL Domain-Containing ProteinsMyelin ProteinsNeoplasmsT-LymphocytesHumansImmunityImmunotherapyB7-H1 AntigenCMTM6 protein, humanMARVEL Domain-Containing ProteinsMyelin Proteins
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