Platelets control liver tumor growth through P2Y12-dependent CD40L release in NAFLD.
Platelets control liver tumor growth through P2Y12-dependent CD40L release in NAFLD.
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DOI：
10.1016/j.ccell.2022.08.004
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发表时间：
2022-09-12
期刊：
影响因子：
50.3
通讯作者：
Greten, Tim F.
中科院分区：
文献类型：
--
作者：
Ma, Chi;Fu, Qiong;Diggs, Laurence P.;Mcvey, John C.;McCallen, Justin;Wabitsch, Simon;Ruf, Benjamin;Brown, Zachary;Heinrich, Bernd;Zhang, Qianfei;Rosato, Umberto;Wang, Sophie;Cui, Linda;Berzofsky, Jay A.;Kleiner, David E.;Bosco, Dale B.;Wu, Long-Jun;Lai, Chunwei Walter;Rotman, Yaron;Xie, Changqing;Korangy, Firouzeh;Greten, Tim F.
血小板是免疫系统中经常被忽视的组成部分，已被证明可以促进肿瘤的生长。非酒精性脂肪性肝病(NAFLD)是西方国家的常见病，患肝细胞癌的风险也在增加。出乎意料的是，我们观察到血小板可以抑制NAFLD小鼠已建立的肝癌的生长。通过对P2Y12的药理抑制和遗传耗竭以及体内输注WT或CD40L的−/−，我们证明了血小板的抗肿瘤功能是通过依赖于P2Y12的CD40L的释放而介导的，从而导致CD40受体激活CD8+T细胞。与抑制P2Y12不同，用阿司匹林阻断血小板既不能阻止血小板CD40L的释放，也不能加速NAFLD小鼠的肝细胞癌。在肝转移模型中也观察到了类似的结果。总之，我们的研究揭示了血小板在肿瘤调节中的复杂作用。对伴有NAFLD的肝癌患者可考虑不抑制CD40L释放的抗血小板治疗。抗血小板治疗与减少肝癌有关。非酒精性脂肪肝是一种增加患肝癌风险的疾病，众所周知，它可以激活血小板。出乎意料的是，马云等人。研究发现，血小板在肿瘤调节中具有复杂的作用，可通过释放依赖于P2Y12的CD40L来增强CD8+T细胞依赖的抗肿瘤免疫。
Platelets, the often-overlooked component of the immune system, have been shown to promote tumor growth. Nonalcoholic 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 growth of established HCC in NAFLD mice. Through pharmacological inhibition and genetic depletion of P2Y12 as well as in vivo transfusion of 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. 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. Anti-platelet therapy is associated with reduced liver cancer. NAFLD, a rising risk for liver cancer, is known to activate platelets. Unexpectedly, Ma et al. found that platelets have a complex role in tumor regulation and can enhance CD8+ T cell-dependent anti-tumor immunity through P2Y12-dependent CD40L release from platelets.
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DOI：
10.4049/jimmunol.1302187
发表时间：
2013-12-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cummings HE;Liu T;Feng C;Laidlaw TM;Conley PB;Kanaoka Y;Boyce JA
通讯作者：
Boyce JA
影响因子：
39
作者：
Lee, Teng-Yu;Hsu, Yao-Chun;Wu, Chun-Ying
通讯作者：
Wu, Chun-Ying
影响因子：
29.4
作者：
Heinrich B;Brown ZJ;Diggs LP;Vormehr M;Ma C;Subramanyam V;Rosato U;Ruf B;Walz JS;McVey JC;Wabitsch S;Fu Q;Yu SJ;Zhang Q;Lai CW;Sahin U;Greten TF
通讯作者：
Greten TF
影响因子：
50.3
作者：
Labelle M;Begum S;Hynes RO
通讯作者：
Hynes RO
影响因子：
4.6
作者：
AuBuchon, J. P.;de Wildt-Eggen, J.;Dumont, L. J.
通讯作者：
Dumont, L. J.