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Interactions between cancer cells and immune cells drive transitions to mesenchymal-like states in glioblastoma.
Hara, Toshiro; Chanoch-Myers, Rony; Mathewson, Nathan D; Myskiw, Chad; Atta, Lyla; Bussema, Lillian; Eichhorn, Stephen W; Greenwald, Alissa C; Kinker, Gabriela S; Rodman, Christopher; Gonzalez Castro, L Nicolas; Wakimoto, Hiroaki; Rozenblatt-Rosen, Orit; Zhuang, Xiaowei; Fan, Jean; Hunter, Tony; Verma, Inder M; Wucherpfennig, Kai W; Regev, Aviv; Suvà, Mario L; Tirosh, Itay.
Affiliation
  • Hara T; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Laboratory o
  • Chanoch-Myers R; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
  • Mathewson ND; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Cancer Immunology and Virology, Department of Microbiology and Immunobiology, Department of Neurology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Myskiw C; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Atta L; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Bussema L; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Eichhorn SW; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA.
  • Greenwald AC; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
  • Kinker GS; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel; Department of Physiology, Institute of Bioscience, University of Sao Paulo, Sao Paulo, Brazil.
  • Rodman C; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Gonzalez Castro LN; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department o
  • Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
  • Rozenblatt-Rosen O; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Zhuang X; Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA; Department of Chemistry and Chemical Biology, Department of Physics, Harvard University, Cambridge, MA 02138, USA.
  • Fan J; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
  • Hunter T; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Verma IM; Laboratory of Genetics, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
  • Wucherpfennig KW; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Cancer Immunology and Virology, Department of Microbiology and Immunobiology, Department of Neurology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02215, USA.
  • Regev A; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Suvà ML; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA. Electronic a
  • Tirosh I; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel. Electronic address: itayt@weizmann.ac.il.
Cancer Cell ; 39(6): 779-792.e11, 2021 06 14.
Article in En | MEDLINE | ID: mdl-34087162
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / T-Lymphocytes / Glioblastoma / Tumor-Associated Macrophages Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2021 Document type: Article Country of publication: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Brain Neoplasms / T-Lymphocytes / Glioblastoma / Tumor-Associated Macrophages Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2021 Document type: Article Country of publication: United States