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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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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]
Número total de Autores: 21
Afiliação do(s) autor(es):
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[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
Número total de Afiliações: 19
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