Research ArticleCancer

Thrombin contributes to cancer immune evasion via proteolysis of platelet-bound GARP to activate LTGF-β

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Science Translational Medicine  08 Jan 2020:
Vol. 12, Issue 525, eaay4860
DOI: 10.1126/scitranslmed.aay4860

Targeting platelets’ darker side

High numbers of platelets can be observed in the setting of advanced cancer, increasing the risk of blood clots. Metelli et al. now demonstrate that platelets also play a more direct role in cancer-associated damage, contributing to tumor growth and immune escape. Thrombin, a serum protein involved in blood coagulation, detaches a cytokine called TGF-β1 from its binding sites on the platelet surface. This results in the release of active TGF-β1, which suppresses the antitumor immune response. The authors also identified a drug that could be repurposed to inhibit this process of TGF-β1 release and demonstrated its efficacy in treating immunocompetent mouse models of cancer.

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