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Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39.
Takenaka, Maisa C; Gabriely, Galina; Rothhammer, Veit; Mascanfroni, Ivan D; Wheeler, Michael A; Chao, Chun-Cheih; Gutiérrez-Vázquez, Cristina; Kenison, Jessica; Tjon, Emily C; Barroso, Andreia; Vandeventer, Tyler; de Lima, Kalil Alves; Rothweiler, Sonja; Mayo, Lior; Ghannam, Soufiene; Zandee, Stephanie; Healy, Luke; Sherr, David; Farez, Mauricio F; Prat, Alexandre; Antel, Jack; Reardon, David A; Zhang, Hailei; Robson, Simon C; Getz, Gad; Weiner, Howard L; Quintana, Francisco J.
Afiliação
  • Takenaka MC; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Gabriely G; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Rothhammer V; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Mascanfroni ID; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Wheeler MA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Chao CC; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Gutiérrez-Vázquez C; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Kenison J; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Tjon EC; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Barroso A; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Vandeventer T; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • de Lima KA; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Rothweiler S; Divisions of Gastroenterology, Hepatology and Transplantation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Mayo L; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
  • Ghannam S; Neuroimmunology Research Lab., Center for Excellence in Neuromics, Department of Neuroscience, Université de Montréal, Montréal, Québec, Canada.
  • Zandee S; Neuroimmunology Research Lab., Center for Excellence in Neuromics, Department of Neuroscience, Université de Montréal, Montréal, Québec, Canada.
  • Healy L; Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
  • Sherr D; Dept of Environmental Health, Boston University School of Public Health, Boston, MA, USA.
  • Farez MF; Center for Research on Neuroimmunological Diseases (CIEN), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina.
  • Prat A; Center for Epidemiology, Biostatistics and Public Health (CEBES), Raúl Carrea Institute for Neurological Research (FLENI), Buenos Aires, Argentina.
  • Antel J; Neuroimmunology Research Lab., Center for Excellence in Neuromics, Department of Neuroscience, Université de Montréal, Montréal, Québec, Canada.
  • Reardon DA; Neuroimmunology Unit, Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University, Montreal, Québec, Canada.
  • Zhang H; Center for Neuro-Oncology, Dana Farber Cancer Institute, Brigham and Women's Hospital, Boston, MA, USA.
  • Robson SC; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Getz G; Divisions of Gastroenterology, Hepatology and Transplantation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
  • Weiner HL; The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Quintana FJ; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Nat Neurosci ; 22(5): 729-740, 2019 05.
Article em En | MEDLINE | ID: mdl-30962630
Tumor-associated macrophages (TAMs) play an important role in the immune response to cancer, but the mechanisms by which the tumor microenvironment controls TAMs and T cell immunity are not completely understood. Here we report that kynurenine produced by glioblastoma cells activates aryl hydrocarbon receptor (AHR) in TAMs to modulate their function and T cell immunity. AHR promotes CCR2 expression, driving TAM recruitment in response to CCL2. AHR also drives the expression of KLF4 and suppresses NF-κB activation in TAMs. Finally, AHR drives the expression of the ectonucleotidase CD39 in TAMs, which promotes CD8+ T cell dysfunction by producing adenosine in cooperation with CD73. In humans, the expression of AHR and CD39 was highest in grade 4 glioma, and high AHR expression was associated with poor prognosis. In summary, AHR and CD39 expressed in TAMs participate in the regulation of the immune response in glioblastoma and constitute potential targets for immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apirase / Neoplasias Encefálicas / Linfócitos T / Antígenos CD / Receptores de Hidrocarboneto Arílico / Glioblastoma / Cinurenina / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apirase / Neoplasias Encefálicas / Linfócitos T / Antígenos CD / Receptores de Hidrocarboneto Arílico / Glioblastoma / Cinurenina / Macrófagos Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article