ArticleOncoimmunology2020
ADAM10 and ADAM17 cleave PD-L1 to mediate PD-(L)1 inhibitor resistance.
Article in Oncoimmunology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 7 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
82 citing papers in PubMed, 7 syntheses or guidelines pooled it.
- Soluble PD-L1 changes in advanced non-small cell lung cancer patients treated with PD-1 inhibitors: an individual patient data meta-analysis.Frontiers in immunology · 2023Pooled it
- Prognostic value of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) for hepatocellular carcinoma: a systematic review and meta-analysis.Cancer immunology, immunotherapy : CII · 2022Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 5: Epigenetic Regulation of PD-L1.International journal of molecular sciences · 2021Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 3: PD-L1, Intracellular Signaling Pathways and Tumor Microenvironment.International journal of molecular sciences · 2021Pooled it
- Pooled it
- Pooled it
- What Do We Have to Know about PD-L1 Expression in Prostate Cancer? A Systematic Literature Review. Part 4: Experimental Treatments in Pre-Clinical Studies (Cell Lines and Mouse Models).International journal of molecular sciences · 2021Pooled it
- Neoadjuvant cobimetinib and atezolizumab with or without vemurafenib for high-risk operable Stage III melanoma: the Phase II NeoACTIVATE trial.Nature communications · 2024Trial
- Trial
- Association of ADAM17 expression with CD4 + and CD8 + tumor-infiltrating lymphocytes in adrenocortical carcinoma and benign adrenal adenoma.Endocrine · 2026Article
- PD-L1 in Ovarian Cancer: Immune Evasion, Tumor-Intrinsic Signaling, and Chemoresistance.Cancer medicine · 2026Review
- Pan-cancer 8q24 amplification predicts primary immunotherapy resistance and therapeutic vulnerabilities.iScience · 2026Article
- Nuclear PD-L1: an emerging oncogenic driver and promising therapeutic target in cancer.Journal of biomedical science · 2026Review
- Multimodal activity-affinity assay of ADAM-10 extracellular vesicles in untreated plasma reveals metastatic stage of colorectal cancer.Biosensors & bioelectronics · 2026Article
- ADAMDEC1-driven CCL2-CCR2-PD-1 axis in esophageal squamous cell carcinoma: a dual threat of O-GlcNAcylation and mCellular oncology (Dordrecht, Netherlands) · 2026Article
- The hypoxic ECM and neutrophils in MIBC immunotherapy resistance.Nature reviews. Urology · 2026Review
- HBx Promotes Liver Cancer Cells to Escape NK-92 Cell Attack by Mediating ADAM10 to Enzyme Cut MICA/B Shedding From Cancer Cell Membrane.Journal of cellular and molecular medicine · 2026Article
- Post-translational modifications of immune checkpoints: molecular mechanisms, tumor microenvironment remodeling, and therapeutic implications.Journal of biomedical science · 2026Review
- Depletion of Soluble PD-L1 with Engineered Nanoparticles Promotes Antitumor Immunity and Tumor Control.International journal of nanomedicine · 2026Article
- Assessment of soluble PD-L1 in septic shock in relation to immunosuppressive phenotypes.Annals of intensive care · 2026Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors.
Funding
Abstract
ADAM10 and ADAM17 expression and soluble PD-L1 (sPD-L1) predict poor prognosis in many malignancies, including in patients treated with PD-(L)1 inhibitors. The mechanism of soluble PD-L1 production and its effects are unknown. Here we uncover a novel mechanism of ADAM10- and ADAM17-mediated resistance to PD-(L)1 inhibitors. ADAM10 and ADAM17 cleave PD-L1 from the surface of malignant cells and extracellular vesicles. This cleavage produces an active sPD-L1 fragment that induces apoptosis in CD8 + T cells and compromises the killing of tumor cells by CD8 + T cells. Reduced tumor site PD-L1 protein-to-mRNA ratios predict poor outcomes and are correlated with elevated ADAM10 and ADAM17 expression in multiple cancers. These results may explain the discordance between PD-L1 immunohistochemistry and PD-(L)1 inhibitor response. Thus, including ADAM10 and ADAM17 tissue staining may improve therapy selection. Furthermore, treatment with an ADAM10/ADAM17 inhibitor may abrogate PD-(L)1 inhibitor resistance and improve clinical responses to PD-(L)1 immunotherapy.
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