肿瘤抑制因子
间充质干细胞
肿瘤微环境
免疫系统
癌症研究
癌细胞
胶质瘤
细胞生物学
生物
癌症
免疫学
细胞因子
白细胞介素6
遗传学
作者
Toshiro Hara,Rony Chanoch-Myers,Nathan D. Mathewson,Chad Myskiw,Lyla Atta,Lillian Bussema,Stephen W. Eichhorn,Alissa C. Greenwald,Gabriela Sarti Kinker,Christopher Rodman,Luis 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
出处
期刊:Cancer Cell
[Elsevier]
日期:2021-06-01
卷期号:39 (6): 779-792.e11
被引量:238
标识
DOI:10.1016/j.ccell.2021.05.002
摘要
The mesenchymal subtype of glioblastoma is thought to be determined by both cancer cell-intrinsic alterations and extrinsic cellular interactions, but remains poorly understood. Here, we dissect glioblastoma-to-microenvironment interactions by single-cell RNA sequencing analysis of human tumors and model systems, combined with functional experiments. We demonstrate that macrophages induce a transition of glioblastoma cells into 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 (OSMR or LIFR) in complex with GP130 on glioblastoma cells and activates STAT3. We show that MES-like glioblastoma states are also associated with increased expression of a mesenchymal program in macrophages and with increased cytotoxicity of T cells, highlighting extensive alterations of the immune microenvironment with potential therapeutic implications.
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