TAMI-12. CANCER-IMMUNE CELL INTERACTIONS DRIVE TRANSITIONS TO MESENCHYMAL-LIKE STATES IN GLIOBLASTOMA. (12th November 2021)

• Record Type: Journal Article
• Authors: Hara, Toshiro; Chanoch-Myers, Rony; Mathewson, Nathan; Myskiw, Chad; Atta, Lyla; Bussema, Lillian; Eichhorn, Stephen; Greenwald, Alissa; Kinker, Gabriela; Rodman, Christopher; Castro, L Nicolas Gonzalez; Wakimoto, Hiroaki; Rozenblatt-Rosen, Orit; Zhuang, Xiaowei; Fan, Jean; Hunter, Tony; Verma, Inder; Wucherpfennig, Kai; Regev, Aviv; Suva, Mario; Tirosh, Itay
• Is Part Of: Neuro-oncology. Volume 23: Supplement 6(2021)
• Page Start: vi200
• Page End: vi200
• Publication Date: 2021-11-12
• Subjects: Brain Neoplasms -- Periodicals; Brain -- Tumors -- Periodicals; Brain -- Cancer -- Periodicals; Nervous system -- Cancer -- Periodicals; 616.99481
• DOI: 10.1093/neuonc/noab196.796
• Languages: English
• ISSNs: 1522-8517

Abstract

Abstract: Communication between cancer cells and immune cells is a key determinant of the glioblastoma ecosystem and its response to therapies, but remains poorly understood. Here we leveraged single-cell RNA-sequencing (scRNA-seq) of human samples and mouse models, deconvolution analysis of bulk specimens from The Cancer Genome Atlas (TCGA) and functional approaches to dissect cellular states and cross-talk in glioblastoma. 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) and its cognate receptor OSMR on glioblastoma cells. We show that MES-like glioblastoma states are associated with increased T cells cytotoxicity and potentially with better clinical response to immunotherapies. Overall, our work dissects the cellular interactions within the glioblastoma microenvironment, with potential implications for therapies.