Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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

doi:10.1016/j.ccell.2021.05.002

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

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 SuvàItay Tirosh

Department of Molecular Cell Biology

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	779-792.e11
Journal	Cancer Cell
Volume	39
Issue number	6
DOIs	https://doi.org/10.1016/j.ccell.2021.05.002
State	Published - 14 Jun 2021

Keywords

GBM
OSM
glioblastoma
macrophage
mesenchymal
scRNA-seq
tumor microenvironment

All Science Journal Classification (ASJC) codes

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ccell.2021.05.002

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Hara, T., Chanoch-Myers, R., Mathewson, N. D., Myskiw, C., Atta, L., Bussema, L., Eichhorn, S. W., Greenwald, A. C., Kinker, G. S., Rodman, C., Gonzalez Castro, L. N., Wakimoto, H., Rozenblatt-Rosen, O., Zhuang, X., Fan, J., Hunter, T., Verma, I. M., Wucherpfennig, K. W., Regev, A., ... Tirosh, I. (2021). Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma. Cancer Cell, 39(6), 779-792.e11. https://doi.org/10.1016/j.ccell.2021.05.002

@article{920b245f8a344a90b6af17e0aa637d6c,

title = "Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma",

abstract = "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.",

keywords = "GBM, OSM, glioblastoma, macrophage, mesenchymal, scRNA-seq, tumor microenvironment",

author = "Toshiro Hara and Rony Chanoch-Myers and Mathewson, \{Nathan D\} and Chad Myskiw and Lyla Atta and Lillian Bussema and Eichhorn, \{Stephen W\} and Greenwald, \{Alissa C\} and Kinker, \{Gabriela S\} and Christopher Rodman and \{Gonzalez Castro\}, \{L. Nicolas\} and Hiroaki Wakimoto and Orit Rozenblatt-Rosen and Xiaowei Zhuang and Jean Fan and Tony Hunter and Verma, \{Inder M\} and Wucherpfennig, \{Kai W\} and Aviv Regev and Suv{\`a}, \{Mario L\} and Itay Tirosh",

note = "Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2021",

month = jun,

day = "14",

doi = "10.1016/j.ccell.2021.05.002",

language = "الإنجليزيّة",

volume = "39",

pages = "779--792.e11",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "6",

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Hara, T, Chanoch-Myers, R, Mathewson, ND, Myskiw, C, Atta, L, Bussema, L, Eichhorn, SW, Greenwald, AC, Kinker, GS, Rodman, C, Gonzalez Castro, LN, Wakimoto, H, Rozenblatt-Rosen, O, Zhuang, X, Fan, J, Hunter, T, Verma, IM, Wucherpfennig, KW, Regev, A, Suvà, ML & Tirosh, I 2021, 'Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma', Cancer Cell, vol. 39, no. 6, pp. 779-792.e11. https://doi.org/10.1016/j.ccell.2021.05.002

TY - JOUR

T1 - Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

AU - Hara, Toshiro

AU - Chanoch-Myers, Rony

AU - Mathewson, Nathan D

AU - Myskiw, Chad

AU - Atta, Lyla

AU - Bussema, Lillian

AU - Eichhorn, Stephen W

AU - Greenwald, Alissa C

AU - Kinker, Gabriela S

AU - Rodman, Christopher

AU - Gonzalez Castro, L. Nicolas

AU - Wakimoto, Hiroaki

AU - Rozenblatt-Rosen, Orit

AU - Zhuang, Xiaowei

AU - Fan, Jean

AU - Hunter, Tony

AU - Verma, Inder M

AU - Wucherpfennig, Kai W

AU - Regev, Aviv

AU - Suvà, Mario L

AU - Tirosh, Itay

PY - 2021/6/14

Y1 - 2021/6/14

N2 - 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.

AB - 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.

KW - GBM

KW - OSM

KW - glioblastoma

KW - macrophage

KW - mesenchymal

KW - scRNA-seq

KW - tumor microenvironment

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U2 - 10.1016/j.ccell.2021.05.002

DO - 10.1016/j.ccell.2021.05.002

M3 - مقالة

C2 - 34087162

SN - 1535-6108

VL - 39

SP - 779-792.e11

JO - Cancer Cell

JF - Cancer Cell

IS - 6

ER -

Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma

Abstract

Keywords

All Science Journal Classification (ASJC) codes

UN SDGs

Access to Document

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