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Glutamine blockade induces divergent metabolic programs to overcome tumor immune evasion.
Leone, Robert D; Zhao, Liang; Englert, Judson M; Sun, Im-Meng; Oh, Min-Hee; Sun, Im-Hong; Arwood, Matthew L; Bettencourt, Ian A; Patel, Chirag H; Wen, Jiayu; Tam, Ada; Blosser, Richard L; Prchalova, Eva; Alt, Jesse; Rais, Rana; Slusher, Barbara S; Powell, Jonathan D.
Afiliação
  • Leone RD; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Zhao L; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Englert JM; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Sun IM; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Oh MH; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Sun IH; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Arwood ML; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Bettencourt IA; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Patel CH; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Wen J; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Tam A; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Blosser RL; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA.
  • Prchalova E; Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Alt J; Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Rais R; Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Slusher BS; Johns Hopkins Drug Discovery, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
  • Powell JD; The Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD 21287, USA. poweljo@jhmi.edu.
Science ; 366(6468): 1013-1021, 2019 11 22.
Article em En | MEDLINE | ID: mdl-31699883
The metabolic characteristics of tumors present considerable hurdles to immune cell function and cancer immunotherapy. Using a glutamine antagonist, we metabolically dismantled the immunosuppressive microenvironment of tumors. We demonstrate that glutamine blockade in tumor-bearing mice suppresses oxidative and glycolytic metabolism of cancer cells, leading to decreased hypoxia, acidosis, and nutrient depletion. By contrast, effector T cells responded to glutamine antagonism by markedly up-regulating oxidative metabolism and adopting a long-lived, highly activated phenotype. These divergent changes in cellular metabolism and programming form the basis for potent antitumor responses. Glutamine antagonism therefore exposes a previously undefined difference in metabolic plasticity between cancer cells and effector T cells that can be exploited as a "metabolic checkpoint" for tumor immunotherapy.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Azo / Caproatos / Imunoterapia Adotiva / Evasão Tumoral / Glutamina / Neoplasias Experimentais Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Compostos Azo / Caproatos / Imunoterapia Adotiva / Evasão Tumoral / Glutamina / Neoplasias Experimentais Idioma: En Ano de publicação: 2019 Tipo de documento: Article