ArticleHepatology communications2022
Inhibition of CMTM4 Sensitizes Cholangiocarcinoma and Hepatocellular Carcinoma to T Cell-Mediated Antitumor Immunity Through PD-L1.
Article in Hepatology communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 39 citations in OpenAlex.
- Research progress ofFrontiers in immunology · 2026Review
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Article
- Inhibiting CMTM4 reverses the immunosuppressive function of myeloid-derived suppressor cells and augments immunotherapy response in cervical cancer.Journal for immunotherapy of cancer · 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
- Comprehensive analysis of CMTM family and immune infiltration in esophageal carcinoma.PloS one · 2025Article
- Immunotherapy combined with targeted therapy and transcatheter arterial chemoembolization: a promising approach for advanced liver cancer.American journal of translational research · 2025Article
- Review
- Construction of a prognostic model for triple-negative breast cancer based on immune-related genes, and associations between the tumor immune microenvironment and immunological therapy.Cancer medicine · 2023Article
- TIMELESS upregulates PD-L1 expression and exerts an immunosuppressive role in breast cancer.Journal of translational medicine · 2023Article
- Article
- [Advances in the Study of Chemokine-like Factor Superfamily Members in Tumors].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2023Review
- Advances in molecular and cell therapy for immunotherapy of cholangiocarcinoma.Frontiers in oncology · 2023Review
- Impact of immune tolerance mechanisms on the efficacy of immunotherapy in primary and secondary liver cancers.Translational gastroenterology and hepatology · 2023Review
- Current Opinions on the Relationship Between CMTM Family and Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Review
- The current status and future of PD-L1 in liver cancer.Frontiers in immunology · 2023Review
- Role of chemokine-like factor 1 as an inflammatory marker in diseases.Frontiers in immunology · 2023Review
- Prognostic significance and immune characteristics of CMTM4 in hepatocellular carcinoma.BMC cancer · 2022Article
- The clinical and prognostic significance of CMTM6/PD-L1 in oncology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2022Review
- CMTM6 and CMTM4 as two novel regulators of PD-L1 modulate the tumor microenvironment.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Liver cancers consist primarily of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). Immune checkpoint inhibitors have emerged as promising therapeutic agents against liver cancers. Programmed cell death protein 1 (PD-1) is an immunoinhibitory receptor present on T cells that interacts with its ligand programmed death-ligand 1 (PD-L1) found on cancer cells. Blocking PD-1/PD-L1 binding improves T-cell survival, proliferation and cytotoxicity, which enhances their antitumor activity. Better understanding of the molecular mechanisms governing PD-1/PD-L1 response is essential to the development of predictive markers and therapeutic combinations that could improve the efficiency of anti-PD-1/PD-L1 treatment. Chemokine-like factor (CKLF)-like MARVEL transmembrane domain-containing 6 (CMTM6) has been recently identified as a major regulator of PD-L1. Another member in the CMTM family, CKLF-like MARVEL transmembrane domain-containing 4 (CMTM4), has been shown to compensate for the effects of CMTM6 when CMTM6 is lost. Interestingly, we found that CMTM4 is the major regulator of PD-L1 in the context of liver cancer. Up-regulated CMTM4 in patients with HCC and ICC is associated with poor patient survival, potentially due to its function in stabilizing PD-L1 expression, hence facilitating escape from T cell-mediated cytotoxicity. We confirmed the role of CMTM4 as a positive regulator of PD-L1 in multiple HCC and ICC cell lines and demonstrated that CMTM4 stabilizes PD-L1 through posttranslational mechanisms. In vivo, suppression of Cmtm4 inhibited HCC growth and increased CD8
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