ArticleNature2017
Identification of CMTM6 and CMTM4 as PD-L1 protein regulators.
Article in Nature, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 448 papers.
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The trial behind it
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Who cites it
448 citing papers in PubMed, 693 citations in OpenAlex.
- Role of CMTM6 in disease pathogenesis and clinical translation potential (Review).Molecular medicine reports · 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
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 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
- Activation of the endocytosis pathway stratifies subtypes and therapeutic sensitivity in colorectal cancer.Research square · 2026Article
- Genetic Interruption of PD-1/PD-L1 as an Alternative Means for Immune Checkpoint Blockade in Cancer: A Review.Pharmaceutics · 2026Review
- 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
- ATF4 promotes immune evasion in oral squamous cell carcinoma by suppressing autophagic PD-L1 degradation.Journal for immunotherapy of cancer · 2026Article
- Cell surface interactome analysis identifies TSPAN4 as a negative regulator of PD-L1 in melanoma.Molecular oncology · 2026Article
- HE4 drives PD-L1 expression in myeloid cells via IFN-γR-JAK-STAT3 signaling to promote tumor immune evasion.Cell reports. Medicine · 2026Article
- Review
- TRIM21-mediated degradation of HILPDA overcomes anti-PD-1 immunotherapy resistance in breast cancer by limiting PD-L1 palmitoylation.Oncogene · 2026Article
- MAVS as a Key Regulator of Tumor Proliferation, Survival, the Tumor Microenvironment, and Immunity.Biomolecules · 2026Article
- Multimodal imaging reveals a lysosomal drug reservoir that drives heterogeneous distribution of PARP inhibitors.Nature communications · 2026Article
- Regulation of natural killer cell infiltration and tumor progression by CMTM6 in gastric cancer.BMC cancer · 2026Article
- Strategies to target PD-1/PD-L1 in the tumor microenvironment.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- CMTM6 suppresses cell-surface expression of death receptor FAS in mice but not in humans.EMBO reports · 2026Article
388 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The clinical benefit for patients with diverse types of metastatic cancers that has been observed upon blockade of the interaction between PD-1 and PD-L1 has highlighted the importance of this inhibitory axis in the suppression of tumour-specific T-cell responses. Notwithstanding the key role of PD-L1 expression by cells within the tumour micro-environment, our understanding of the regulation of the PD-L1 protein is limited. Here we identify, using a haploid genetic screen, CMTM6, a type-3 transmembrane protein of previously unknown function, as a regulator of the PD-L1 protein. Interference with CMTM6 expression results in impaired PD-L1 protein expression in all human tumour cell types tested and in primary human dendritic cells. Furthermore, through both a haploid genetic modifier screen in CMTM6-deficient cells and genetic complementation experiments, we demonstrate that this function is shared by its closest family member, CMTM4, but not by any of the other CMTM members tested. Notably, CMTM6 increases the PD-L1 protein pool without affecting PD-L1 (also known as CD274) transcription levels. Rather, we demonstrate that CMTM6 is present at the cell surface, associates with the PD-L1 protein, reduces its ubiquitination and increases PD-L1 protein half-life. Consistent with its role in PD-L1 protein regulation, CMTM6 enhances the ability of PD-L1-expressing tumour cells to inhibit T cells. Collectively, our data reveal that PD-L1 relies on CMTM6/4 to efficiently carry out its inhibitory function, and suggest potential new avenues to block this pathway.
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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.