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Oxygen Sensing by T Cells Establishes an Immunologically Tolerant Metastatic Niche.
Clever, David; Roychoudhuri, Rahul; Constantinides, Michael G; Askenase, Michael H; Sukumar, Madhusudhanan; Klebanoff, Christopher A; Eil, Robert L; Hickman, Heather D; Yu, Zhiya; Pan, Jenny H; Palmer, Douglas C; Phan, Anthony T; Goulding, John; Gattinoni, Luca; Goldrath, Ananda W; Belkaid, Yasmine; Restifo, Nicholas P.
Afiliação
  • Clever D; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Medical Scientist Training Program, The Ohio State University College of Medicine, Columbus, OH 43210, USA. Electronic address: david.clever@osumc.edu.
  • Roychoudhuri R; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Laboratory of Lymphocyte Signaling and Development, Babraham Institute, Cambridge CB22 3AT, UK.
  • Constantinides MG; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
  • Askenase MH; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA.
  • Sukumar M; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Klebanoff CA; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell Engineering and Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
  • Eil RL; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Hickman HD; Laboratory of Viral Diseases, NIAID, NIH, Bethesda, MD 20892, USA.
  • Yu Z; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Pan JH; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Palmer DC; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Phan AT; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Goulding J; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Gattinoni L; Experimental Transplantation Immunology Branch, NCI, NIH, Bethesda, MD 20892, USA.
  • Goldrath AW; Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
  • Belkaid Y; Mucosal Immunology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, MD 20892, USA; NIAID Microbiome Program Initiative, NIAID/NIH, Bethesda, MD 20892, USA.
  • Restifo NP; Surgery Branch, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD 20892, USA; Center for Cell-based Therapy, National Cancer Institute, National Institutes of Health (NIH), Bethesda, MD 20892, USA. Electronic address: restifo@nih.gov.
Cell ; 166(5): 1117-1131.e14, 2016 Aug 25.
Article em En | MEDLINE | ID: mdl-27565342
Cancer cells must evade immune responses at distant sites to establish metastases. The lung is a frequent site for metastasis. We hypothesized that lung-specific immunoregulatory mechanisms create an immunologically permissive environment for tumor colonization. We found that T-cell-intrinsic expression of the oxygen-sensing prolyl-hydroxylase (PHD) proteins is required to maintain local tolerance against innocuous antigens in the lung but powerfully licenses colonization by circulating tumor cells. PHD proteins limit pulmonary type helper (Th)-1 responses, promote CD4(+)-regulatory T (Treg) cell induction, and restrain CD8(+) T cell effector function. Tumor colonization is accompanied by PHD-protein-dependent induction of pulmonary Treg cells and suppression of IFN-γ-dependent tumor clearance. T-cell-intrinsic deletion or pharmacological inhibition of PHD proteins limits tumor colonization of the lung and improves the efficacy of adoptive cell transfer immunotherapy. Collectively, PHD proteins function in T cells to coordinate distinct immunoregulatory programs within the lung that are permissive to cancer metastasis. PAPERCLIP.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxigênio / Linfócitos T Reguladores / Linfócitos T CD8-Positivos / Prolil Hidroxilases / Pulmão / Neoplasias Pulmonares Idioma: En Ano de publicação: 2016 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Oxigênio / Linfócitos T Reguladores / Linfócitos T CD8-Positivos / Prolil Hidroxilases / Pulmão / Neoplasias Pulmonares Idioma: En Ano de publicação: 2016 Tipo de documento: Article