ArticleNature2017
CMTM6 maintains the expression of PD-L1 and regulates anti-tumour immunity.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 598 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
598 citing papers in PubMed, 921 citations in OpenAlex.
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 2026Review
- Post‑translational modification‑governed immune states in cancer immunity: Biomarker implications for checkpoint competence, tumor visibility and immunotherapy resistance (Review).International journal of oncology · 2026Review
- Reprogramming PD-L1 endosomal recycling and lysosomal degradation via engineered exosome-based nanocomposites overcomes immune resistance in lung cancer brain metastasis.Materials today. Bio · 2026Article
- Low circulating miR-5193 promotes PD-L1-mediated immune evasion and relates to immune checkpoint inhibitor response in esophageal cancer.Molecular therapy. Nucleic acids · 2026Article
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- High-Content CRISPR Screening: Methods and Applications.MedComm · 2026Review
- Systemic delivery of stealth adenoviral vector to reinvigorate antitumor immunity by PD-L1 genome editing and TIGIT/CD155 blocking.Fundamental research · 2026Article
- CMTM6 maintains B cell-intrinsic membrane CD40 stability to regulate anti-tumor immunity.Acta pharmaceutica Sinica. B · 2026Article
- PD-L1 in Ovarian Cancer: Immune Evasion, Tumor-Intrinsic Signaling, and Chemoresistance.Cancer medicine · 2026Review
- circZNF148 Drives Glucose Metabolism Reprogramming to Enhance Metastasis and Immune Evasion via HK1 Stabilization in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Regulation of immune checkpoint molecules in cancer immune evasion and therapy.Nature reviews. Cancer · 2026Review
- Inhibiting CXCL12/CXCR4 axis enhances T cell activity in gastric cancer.Cancer gene therapy · 2026Article
- Temporal Dynamics of PD-L1 Surface in RKO Cells: Characterizing the Reversible Impact of the Small-Molecule Dimerizer BMS-202.Biomedicines · 2026Article
- Repurposed ethoxzolamide reprograms antitumor immunity through β-TrCP-dependent PD-L1 ubiquitination.Cell reports. Medicine · 2026Article
- Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies.Biomarker research · 2026Review
- Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer.Research square · 2026Article
- Elevation of Eosinophil Proportion After Pembrolizumab Increases the Risk of Immune-Related Adverse Events in Patients With Bladder Cancer.Cancer medicine · 2026Observational
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- miR-133b induces antitumor immunity in cervical cancer through modulating CMTM6/PD-L1 axis.Molecular genetics and genomics : MGG · 2026Article
- DHHC3 interferes with antitumor immunity in melanoma cells.Oncotarget · 2026Article
538 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
24 authors at 5 institutions in 2 countries.
Funding
Abstract
Cancer cells exploit the expression of the programmed death-1 (PD-1) ligand 1 (PD-L1) to subvert T-cell-mediated immunosurveillance. The success of therapies that disrupt PD-L1-mediated tumour tolerance has highlighted the need to understand the molecular regulation of PD-L1 expression. Here we identify the uncharacterized protein CMTM6 as a critical regulator of PD-L1 in a broad range of cancer cells, by using a genome-wide CRISPR-Cas9 screen. CMTM6 is a ubiquitously expressed protein that binds PD-L1 and maintains its cell surface expression. CMTM6 is not required for PD-L1 maturation but co-localizes with PD-L1 at the plasma membrane and in recycling endosomes, where it prevents PD-L1 from being targeted for lysosome-mediated degradation. Using a quantitative approach to profile the entire plasma membrane proteome, we find that CMTM6 displays specificity for PD-L1. Notably, CMTM6 depletion decreases PD-L1 without compromising cell surface expression of MHC class I. CMTM6 depletion, via the reduction of PD-L1, significantly alleviates the suppression of tumour-specific T cell activity in vitro and in vivo. These findings provide insights into the biology of PD-L1 regulation, identify a previously unrecognized master regulator of this critical immune checkpoint and highlight a potential therapeutic target to overcome immune evasion by tumour cells.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.