ArticleScience translational medicine2020
Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β.
Article in Science translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 3 of them syntheses that pooled it.
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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
85 citing papers in PubMed, 3 syntheses or guidelines pooled it, 130 citations in OpenAlex.
- Synergistic effects of anticoagulants and platelet aggregation inhibitors with immune checkpoint inhibitors in cancer therapy: a comprehensive review of preclinical and clinical evidence.Journal for immunotherapy of cancer · 2026Pooled it
- Concomitant anticoagulants and the survival of cancer patients treated with immune checkpoint inhibitors: a meta-analysis.Scientific reports · 2025Pooled it
- Associations Between Immune-Related Venous Thromboembolism and Efficacy of Immune Checkpoint Inhibitors: A Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/HemostasisPooled it
- Efficacy and safety of low-molecular-weight heparin or rivaroxaban combined with immunotherapy and chemotherapy in the treatment of advanced nonsmall cell lung cancer: a prospective, randomized, controlled clinical study.Cancer immunology, immunotherapy : CII · 2025Trial
- Platelets as non-canonical immune regulatory nodes: orchestrating T cell dysfunction and immunotherapy resistance in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Platelets as regulators of anti-tumor immunity: mechanisms and clinical implications.Cancer metastasis reviews · 2026Review
- Tumor-platelet cross talk in cancer: mechanisms, thrombotic risk, and translational opportunities.Blood advances · 2026Review
- Platelets as localized conduits of TGF-β1 in the tumor microenvironment: implications for cancer progression and therapy.Human cell · 2026Review
- Soft cell-derived hybrid microparticles with platelet decoys for enhanced cancer chemotherapy.Acta pharmaceutica Sinica. B · 2026Article
- Precision immunotherapy for head and neck cancer: therapeutic combinations, biomarker strategies, and translational challenges.Molecular cancer · 2026Review
- TGFβ enhances platelet-breast-cancer-cell interaction and promotes platelet aggregation.The FEBS journal · 2026Article
- Platelets in the tumor microenvironment: potential mediators of immune exclusion and resistance to immune checkpoint inhibitor therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Association between platelet-to-lymphocyte ratio and high risk for prostate cancer among middle-aged and older US men.Scientific reports · 2026Article
- ROS-sensitive liposomal co-delivery of photosensitizer, factor Xa inhibitor, and PD-L1 blockade enhances photodynamic immunotherapy.Theranostics · 2026Article
- A fully human afucosylated anti-GARP antibody PBA-0111 drives anti-tumor immunity through combined ADCC induction and TGF-β1 pathway blockade.Frontiers in immunology · 2026Article
- Bidirectional regulatory mechanisms and therapeutic prospects of tumor hypercoagulable state and immunosuppressive tumor microenvironment.Oncology reviews · 2026Review
- Emerging roles of haemostatic proteins as markers of disease progression and prognosis in breast cancer.Exploration of targeted anti-tumor therapy · 2026Review
- Multifunctional nanoagonist enhances photodynamic therapy-driven in situ cancer vaccination by inhibiting tumor thrombosis.Journal of nanobiotechnology · 2025Article
- Coagulation proteases modulate nucleic acid uptake and cGAS-STING-IFN induction in the tumor microenvironment.JCI insight · 2025Article
- Unveiling the "Dark Matter" of platelet involvement in tumor microenvironment.Journal of pharmaceutical analysis · 2025Review
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
Abstract
Cancer-associated thrombocytosis and high concentrations of circulating transforming growth factor-β1 (TGF-β1) are frequently observed in patients with progressive cancers. Using genetic and pharmacological approaches, we show a direct link between thrombin catalytic activity and release of mature TGF-β1 from platelets. We found that thrombin cleaves glycoprotein A repetitions predominant (GARP), a cell surface docking receptor for latent TGF-β1 (LTGF-β1) on platelets, resulting in liberation of active TGF-β1 from the GARP-LTGF-β1 complex. Furthermore, systemic inhibition of thrombin obliterates TGF-β1 maturation in platelet releasate and rewires the tumor microenvironment toward favorable antitumor immunity, which translates into efficient cancer control either alone or in combination with programmed cell death 1-based immune checkpoint blockade therapy. Last, we demonstrate that soluble GARP and GARP-LTGF-β1 complex are present in the circulation of patients with cancer. Together, our data reveal a mechanism of cancer immune evasion that involves thrombin-mediated GARP cleavage and the subsequent TGF-β1 release from platelets. We propose that blockade of GARP cleavage is a valuable therapeutic strategy to overcome cancer's resistance to immunotherapy.
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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.