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Inhibitory CD161 receptor identified in glioma-infiltrating T cells by single-cell analysis.
Mathewson, Nathan D; Ashenberg, Orr; Tirosh, Itay; Gritsch, Simon; Perez, Elizabeth M; Marx, Sascha; Jerby-Arnon, Livnat; Chanoch-Myers, Rony; Hara, Toshiro; Richman, Alyssa R; Ito, Yoshinaga; Pyrdol, Jason; Friedrich, Mirco; Schumann, Kathrin; Poitras, Michael J; Gokhale, Prafulla C; Gonzalez Castro, L Nicolas; Shore, Marni E; Hebert, Christine M; Shaw, Brian; Cahill, Heather L; Drummond, Matthew; Zhang, Wubing; Olawoyin, Olamide; Wakimoto, Hiroaki; Rozenblatt-Rosen, Orit; Brastianos, Priscilla K; Liu, X Shirley; Jones, Pamela S; Cahill, Daniel P; Frosch, Matthew P; Louis, David N; Freeman, Gordon J; Ligon, Keith L; Marson, Alexander; Chiocca, E Antonio; Reardon, David A; Regev, Aviv; Suvà, Mario L; Wucherpfennig, Kai W.
Afiliação
  • Mathewson ND; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Ashenberg O; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
  • Tirosh I; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
  • Gritsch S; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Perez EM; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA; Department of Systems Biology, Harvard Medical Scho
  • Marx S; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Jerby-Arnon L; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA.
  • Chanoch-Myers R; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 761001, Israel.
  • Hara T; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Richman AR; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Ito Y; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA.
  • Pyrdol J; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Friedrich M; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Schumann K; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München (TUM), Munich, Germany.
  • Poitras MJ; Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Gokhale PC; Experimental Therapeutics Core and Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Gonzalez Castro LN; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospit
  • Shore ME; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Hebert CM; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Shaw B; Departments of Neurology and Radiation Oncology, Divisions of Hematology/Oncology and Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
  • Cahill HL; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Drummond M; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Zhang W; Department of Data Science, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Olawoyin O; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Wakimoto H; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
  • Rozenblatt-Rosen O; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Genentech, South San Francisco, CA, USA.
  • Brastianos PK; Departments of Neurology and Radiation Oncology, Divisions of Hematology/Oncology and Neuro-Oncology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, MA 02114, USA.
  • Liu XS; Department of Data Science, Dana-Farber Cancer Institute, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Jones PS; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
  • Cahill DP; Department of Neurosurgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114 USA.
  • Frosch MP; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Louis DN; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
  • Freeman GJ; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Ligon KL; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.
  • Marson A; Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA, USA; Gladstone Institutes, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
  • Chiocca EA; Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, USA.
  • Reardon DA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: david_reardon@dfci.harvard.edu.
  • Regev A; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Genentech, South San Francisco, CA, USA; Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Department of Biology, MIT, Cambri
  • Suvà ML; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Klarman Cell Observatory, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA; Department of Pathology and Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA. Electronic address: suva.mario@mgh.harvard.edu.
  • Wucherpfennig KW; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA; Department of Immunology, Harvard Medical School, Boston, MA, USA; Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic a
Cell ; 184(5): 1281-1298.e26, 2021 03 04.
Article em En | MEDLINE | ID: mdl-33592174
ABSTRACT
T cells are critical effectors of cancer immunotherapies, but little is known about their gene expression programs in diffuse gliomas. Here, we leverage single-cell RNA sequencing (RNA-seq) to chart the gene expression and clonal landscape of tumor-infiltrating T cells across 31 patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and IDH mutant glioma. We identify potential effectors of anti-tumor immunity in subsets of T cells that co-express cytotoxic programs and several natural killer (NK) cell genes. Analysis of clonally expanded tumor-infiltrating T cells further identifies the NK gene KLRB1 (encoding CD161) as a candidate inhibitory receptor. Accordingly, genetic inactivation of KLRB1 or antibody-mediated CD161 blockade enhances T cell-mediated killing of glioma cells in vitro and their anti-tumor function in vivo. KLRB1 and its associated transcriptional program are also expressed by substantial T cell populations in other human cancers. Our work provides an atlas of T cells in gliomas and highlights CD161 and other NK cell receptors as immunotherapy targets.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Subfamília B de Receptores Semelhantes a Lectina de Células NK / Glioma Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Linfócitos T / Subfamília B de Receptores Semelhantes a Lectina de Células NK / Glioma Limite: Animals Idioma: En Revista: Cell Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Estados Unidos