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Obesity Shapes Metabolism in the Tumor Microenvironment to Suppress Anti-Tumor Immunity.
Ringel, Alison E; Drijvers, Jefte M; Baker, Gregory J; Catozzi, Alessia; García-Cañaveras, Juan C; Gassaway, Brandon M; Miller, Brian C; Juneja, Vikram R; Nguyen, Thao H; Joshi, Shakchhi; Yao, Cong-Hui; Yoon, Haejin; Sage, Peter T; LaFleur, Martin W; Trombley, Justin D; Jacobson, Connor A; Maliga, Zoltan; Gygi, Steven P; Sorger, Peter K; Rabinowitz, Joshua D; Sharpe, Arlene H; Haigis, Marcia C.
Afiliação
  • Ringel AE; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Drijvers JM; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, M
  • Baker GJ; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Catozzi A; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Lewis Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
  • García-Cañaveras JC; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Biomarkers and Precision Medicine Unit, Instituto de Investigación Sanitaria Fundación Hospital La Fe, València 46026, Spain.
  • Gassaway BM; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Miller BC; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Juneja VR; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Nguyen TH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Joshi S; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Yao CH; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Yoon H; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Sage PT; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • LaFleur MW; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Trombley JD; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Jacobson CA; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Maliga Z; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Gygi SP; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
  • Sorger PK; Laboratory of Systems Pharmacology, Harvard Medical School, Boston, MA 02115, USA.
  • Rabinowitz JD; Department of Chemistry, Princeton University, Princeton, NJ 08544, USA; Biomarkers and Precision Medicine Unit, Instituto de Investigación Sanitaria Fundación Hospital La Fe, València 46026, Spain.
  • Sharpe AH; Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA; Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Electronic address: arlene_sharpe@hms.harvard.edu.
  • Haigis MC; Department of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA. Electronic address: marcia_haigis@hms.harvard.edu.
Cell ; 183(7): 1848-1866.e26, 2020 12 23.
Article em En | MEDLINE | ID: mdl-33301708
ABSTRACT
Obesity is a major cancer risk factor, but how differences in systemic metabolism change the tumor microenvironment (TME) and impact anti-tumor immunity is not understood. Here, we demonstrate that high-fat diet (HFD)-induced obesity impairs CD8+ T cell function in the murine TME, accelerating tumor growth. We generate a single-cell resolution atlas of cellular metabolism in the TME, detailing how it changes with diet-induced obesity. We find that tumor and CD8+ T cells display distinct metabolic adaptations to obesity. Tumor cells increase fat uptake with HFD, whereas tumor-infiltrating CD8+ T cells do not. These differential adaptations lead to altered fatty acid partitioning in HFD tumors, impairing CD8+ T cell infiltration and function. Blocking metabolic reprogramming by tumor cells in obese mice improves anti-tumor immunity. Analysis of human cancers reveals similar transcriptional changes in CD8+ T cell markers, suggesting interventions that exploit metabolism to improve cancer immunotherapy.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microambiente Tumoral / Imunidade / Neoplasias / Obesidade Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Microambiente Tumoral / Imunidade / Neoplasias / Obesidade Tipo de estudo: Risk_factors_studies Limite: Animals / Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article