小柯机器人

中山大学李建明等研究人员合作发现，靶向血小板/巨核细胞中的Erbin-线粒体轴可促进B细胞介导的抗肿瘤免疫。2024年1月16日，国际知名学术期刊《细胞—代谢》在线发表了这一成果。

研究人员发现，在结直肠癌患者中，有转移的患者血小板数量明显增加，而在有转移的患者血小板中，Erbin表达量很高。此外，在血小板/巨核细胞（MK）中敲除Erbin可抑制小鼠肺转移，并促进血小板聚集。从机理上讲，Erbin缺陷的血小板线粒体氧化磷酸化增加，并通过取消与促血栓形成蛋白ESAM的相互作用分泌脂质代谢物，如酰基肉碱（Acar）。

值得注意的是，Acar通过对H3K27进行乙酰化表观遗传，增强了B细胞线粒体电子传递链复合物和线粒体氧化磷酸化的活性。通过纳米微粒系统靶向血小板/MK中的Erbin可显著减轻小鼠体内的肺转移。这项研究发现了血小板/MK中的Erbin-线粒体轴，它抑制了B细胞介导的抗肿瘤免疫，并为转移瘤的治疗提供了一条新途径。

据悉，血小板/MK是血液系统的重要组成部分，它们在肿瘤微环境和抗肿瘤免疫中的作用尚不清楚。

附：英文原文

Title: Targeting Erbin-mitochondria axis in platelets/megakaryocytes promotes B cell-mediated antitumor immunity

Author: Zilong Zhang, Xu Xu, Di Zhang, Songsong Zhao, Chuyi Wang, Guilin Zhang, Wenshu Chen, Jinglin Liu, Huimin Gong, Youlutuziayi Rixiati, Shi Li, Tong Shen, Jianming Li

Issue&Volume: 2024-01-16

Abstract: The roles of platelets/megakaryocytes (MKs), the key components in the blood system,in the tumor microenvironment and antitumor immunity are unclear. In patients withcolorectal cancer, the number of platelets was significantly increased in patientswith metastasis, and Erbin expression was highly expressed in platelets from patientswith metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasisin mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient plateletshave increasing mitochondrial oxidative phosphorylation and secrete lipid metaboliteslike acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM.Notably, Acar enhanced the activity of mitochondrial electron transport chain complexand mitochondrial oxidative phosphorylation in B cells by acetylation of H3K27 epigenetically.Targeting Erbin in platelets/MKs by a nanovesicle system dramatically attenuated lungmetastasis in mice in vivo. Our study identifies an Erbin-mitochondria axis in platelets/MKs, which suppressesB cell-mediated antitumor immunity, suggesting a new way for the treatment of metastasis.

DOI: 10.1016/j.cmet.2023.12.020

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(23)00471-0

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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