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

被引：345

作者：

Hara, Toshiro ^{[1
,2
,3
,4
,5
,6
]}

Chanoch-Myers, Rony ^{[7
]}

Mathewson, Nathan D. ^{[5
,8
,9
]}

Myskiw, Chad ^{[6
]}

Atta, Lyla ^{[10
]}

Bussema, Lillian ^{[1
,2
,3
,4
,5
]}

Eichhorn, Stephen W. ^{[11
,12
]}

Greenwald, Alissa C. ^{[7
]}

Kinker, Gabriela S. ^{[7
,13
]}

Rodman, Christopher ^{[1
,2
,3
]}

Castro, L. Nicolas Gonzalez ^{[1
,2
,3
,4
,5
,14
,15
,16
]}

Wakimoto, Hiroaki ^{[3
,17
]}

Rozenblatt-Rosen, Orit ^{[4
,5
,19
]}

Zhuang, Xiaowei ^{[11
,12
]}

Fan, Jean ^{[10
]}

Hunter, Tony ^{[6
]}

Verma, Inder M. ^{[6
]}

Wucherpfennig, Kai W. ^{[5
,8
,9
]}

Regev, Aviv ^{[4
,5
,18
,19
]}

Suva, Mario L. ^{[1
,2
,3
,4
,5
]}

Tirosh, Itay ^{[7
]}

机构：

[1] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA

[2] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 USA

[3] Harvard Med Sch, Boston, MA 02114 USA

[4] Broad Inst Harvard & MIT, Klarman Cell Observ, Cambridge, MA 02142 USA

[5] Broad Inst Harvard & MIT, Cambridge, MA 02142 USA

[6] Salk Inst Biol Studies, Lab Genet, La Jolla, CA 92037 USA

[7] Weizmann Inst Sci, Dept Mol Cell Biol, IL-761001 Rehovot, Israel

[8] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Dept Microbiol & Immunobiol, Dept Neurol, Boston, MA 02215 USA

[9] Harvard Med Sch, Boston, MA 02215 USA

[10] Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA

[11] Harvard Univ, Howard Hughes Med Inst, Cambridge, MA 02138 USA

[12] Harvard Univ, Dept Chem & Chem Biol, Dept Phys, Cambridge, MA 02138 USA

[13] Univ Sao Paulo, Inst Biosci, Dept Physiol, Sao Paulo, Brazil

[14] Brigham & Womens Dana Farber Canc Ctr, Dept Neurol, Boston, MA 02115 USA

[15] Brigham & Womens Dana Farber Canc Ctr, Ctr Neurooncol, Boston, MA 02115 USA

[16] Harvard Med Sch, Boston, MA 02115 USA

[17] Massachusetts Gen Hosp, Dept Neurosurg, Boston, MA 02114 USA

[18] MIT, Koch Inst Integrat Canc Res, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 USA

[19] Genentech Inc, 1 DNA Way, San Francisco, CA USA

来源：

CANCER CELL | 2021年 / 39卷 / 06期

基金：

巴西圣保罗研究基金会; 日本学术振兴会; 以色列科学基金会;

关键词：

ONCOSTATIN-M; RNA-SEQ; T-CELLS; SINGLE; RECEPTOR; SUBTYPES; HETEROGENEITY; EMT; PHENOTYPES; GLIOMAS;

D O I：

10.1016/j.ccell.2021.05.002

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

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.

引用

页码：779 / +

页数：25

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