以色列魏茨曼科学研究所Itay Tirosh和美国哈佛-麻省理工学院Mario L. Suvà研究小组合作发现在胶质母细胞瘤中,癌细胞和免疫细胞之间的相互作用促进细胞向间充质样状态转变。相关论文于2021年6月3日在线发表于国际学术期刊《癌细胞》杂志。
研究人员利用对人类肿瘤和模型系统的单细胞 RNA 测序分析结合功能实验探究了胶质母细胞瘤与微环境的相互作用。研究证明巨噬细胞诱导胶质母细胞瘤细胞转变为间充质样(MES 样)状态。无论在体外还是体内,这种效应是由巨噬细胞诱导的制瘤素 M (OSM) 介导,OSM 与其受体(OSMR 或 LIFR)相互作用,并与胶质母细胞瘤细胞上的 GP130结合激活 STAT3。
研究表明,MES 样胶质母细胞瘤状态也与巨噬细胞中间充质程序表达增加和 T 细胞细胞毒性增加有关,这突出了免疫微环境的广泛改变并具有潜在的治疗意义。
据悉,胶质母细胞瘤的间充质亚型被认为是由癌细胞内在改变和外在细胞相互作用决定的,但对其理解仍知之甚少。
附:英文原文
Title: Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma
Author: Toshiro Hara, Rony Chanoch-Myers, Nathan D. Mathewson, Chad Myskiw, Lyla Atta, Lillian Bussema, Stephen W. Eichhorn, Alissa C. Greenwald, Gabriela S. Kinker, Christopher Rodman, L. Nicolas Gonzalez Castro, Hiroaki Wakimoto, Orit Rozenblatt-Rosen, Xiaowei Zhuang, Jean Fan, Tony Hunter, Inder M. Verma, Kai W. Wucherpfennig, Aviv Regev, Mario L. Suvà, Itay Tirosh
Issue&Volume: 2021-06-03
Abstract: The mesenchymal subtype of glioblastoma is thought to be determined by both cancercell-intrinsic alterations and extrinsic cellular interactions, but remains poorlyunderstood. Here, we dissect glioblastoma-to-microenvironment interactions by single-cellRNA sequencing analysis of human tumors and model systems, combined with functionalexperiments. We demonstrate that macrophages induce a transition of glioblastoma cellsinto mesenchymal-like (MES-like) states. This effect is mediated, both in vitro and in vivo, by macrophage-derived oncostatin M (OSM) that interacts with its receptors (OSMRor LIFR) in complex with GP130 on glioblastoma cells and activates STAT3. We showthat MES-like glioblastoma states are also associated with increased expression ofa mesenchymal program in macrophages and with increased cytotoxicity of T cells, highlightingextensive alterations of the immune microenvironment with potential therapeutic implications.
DOI: 10.1016/j.ccell.2021.05.002
Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(21)00268-3
Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx