| Literature DB >> 36055226 |
Chi Ma1, Qiong Fu1, Laurence P Diggs1, John C McVey2, Justin McCallen1, Simon Wabitsch1, Benjamin Ruf1, Zachary Brown1, Bernd Heinrich3, Qianfei Zhang1, Umberto Rosato1, Sophie Wang1, Linda Cui1, Jay A Berzofsky4, David E Kleiner5, Dale B Bosco6, Long-Jun Wu6, Chunwei Walter Lai7, Yaron Rotman7, Changqing Xie1, Firouzeh Korangy1, Tim F Greten8.
Abstract
Platelets, the often-overlooked component of the immune system, have been shown to promote tumor growth. Non-alcoholic fatty liver disease (NAFLD) is a common disease in the Western world and rising risk for hepatocellular carcinoma (HCC). Unexpectedly, we observed that platelets can inhibit the growth of established HCC in NAFLD mice. Through pharmacological inhibition and genetic depletion of P2Y12 as well as in vivo transfusion of wild-type (WT) or CD40L-/- platelets, we demonstrate that the anti-tumor function of platelets is mediated through P2Y12-dependent CD40L release, which leads to CD8+ T cell activation by the CD40 receptor. Unlike P2Y12 inhibition, blocking platelets with aspirin does not prevent platelet CD40L release nor accelerate HCC in NAFLD mice. Similar findings were observed in liver metastasis models. All together, our study reveals a complex role of platelets in tumor regulation. Anti-platelet treatment without inhibiting CD40L release could be considered for liver cancer patients with NAFLD. Published by Elsevier Inc.Entities:
Keywords: CD40L; HCC; NAFLD; P2Y12; liver metastasis; platelets
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Year: 2022 PMID： 36055226 PMCID： PMC9474605 DOI： 10.1016/j.ccell.2022.08.004
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 38.585