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

Autor(es):Mostrar menos -

Hara, Toshiro ^{[1, 2, 3, 4, 5, 6]} ; Chanoch-Myers, Rony ^[7] ; Mathewson, Nathan D. ^{[4, 8, 9]} ; Myskiw, Chad ^[1] ; Atta, Lyla ^[10] ; Bussema, Lillian ^{[2, 3, 4, 5, 6]} ; Eichhorn, Stephen W. ^{[11, 12]} ; Greenwald, Alissa C. ^[7] ; Kinker, Gabriela S. ^{[13, 7]} ; Rodman, Christopher ^{[2, 3, 5]} ; Castro, L. Nicolas Gonzalez ^{[2, 3, 14, 4, 5, 6, 15, 16]} ; Wakimoto, Hiroaki ^{[2, 17]} ; Rozenblatt-Rosen, Orit ^{[4, 6, 18]} ; Zhuang, Xiaowei ^{[11, 12]} ; Fan, Jean ^[10] ; Hunter, Tony ^[1] ; Verma, Inder M. ^[1] ; Wucherpfennig, Kai W. ^{[4, 8, 9]} ; Regev, Aviv ^{[4, 6, 18, 19]} ; Suva, Mario L. ^{[2, 3, 4, 5, 6]} ; Tirosh, Itay ^[7]

Afiliação do(s) autor(es):Mostrar menos -

^[1] Salk Inst Biol Studies, Lab Genet, La Jolla, CA 92037 - USA

^[2] Harvard Med Sch, Boston, MA 02114 - USA

^[3] Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 - USA

^[4] Broad Inst Harvard & MIT, Cambridge, MA 02142 - USA

^[5] Massachusetts Gen Hosp, Ctr Canc Res, Boston, MA 02114 - USA

^[6] Broad Inst Harvard & MIT, Klarman Cell Observ, Cambridge, MA 02142 - USA

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

^[8] Harvard Med Sch, Boston, MA 02215 - USA

^[9] Dana Farber Canc Inst, Dept Canc Immunol & Virol, Dept Microbiol & Immunobiol, Dept Neurol, 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] Harvard Med Sch, Boston, MA 02115 - USA

^[15] Brigham & Womens Dana Farber Canc Ctr, Dept Neurol, Boston, MA 02115 - USA

^[16] Brigham & Womens Dana Farber Canc Ctr, Ctr Neurooncol, Boston, MA 02115 - USA

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

^[18] Genentech Inc, 1 DNA Way, San Francisco, CA - USA

^[19] MIT, Koch Inst Integrat Canc Res, Dept Biol, Howard Hughes Med Inst, Cambridge, MA 02139 - USA

• Tipo de documento: Artigo Científico
• Fonte: CANCER CELL; v. 39, n. 6, p. 779+, JUN 14 2021.
• Citações Web of Science: 7

Resumo

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. (AU)

• Processo FAPESP: 14/27287-0 - Caracterização do sistema melatonérgico de gliomas humanos e sua implicação sobre o grau de agressividade e invasibilidade tumoral
• Beneficiário: Gabriela Sarti Kinker
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 17/24287-8 - O papel de elementos do microambiente tumoral na plasticidade e heterogeneidade de células malignas
• Beneficiário: Gabriela Sarti Kinker
• Modalidade de apoio: Bolsas no Exterior - Estágio de Pesquisa - Doutorado Direto