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Differential Reliance on Lipid Metabolism as a Salvage Pathway Underlies Functional Differences of T Cell Subsets in Poor Nutrient Environments.

Authors
  • Ecker, Christopher1
  • Guo, Lili2
  • Voicu, Stefana1
  • Gil-de-Gómez, Luis2
  • Medvec, Andrew1
  • Cortina, Luis1
  • Pajda, Jackie3
  • Andolina, Melanie3
  • Torres-Castillo, Maria3
  • Donato, Jennifer L3
  • Mansour, Sarya3
  • Zynda, Evan R3
  • Lin, Pei-Yi3
  • Varela-Rohena, Angel3
  • Blair, Ian A2
  • Riley, James L4
  • 1 Department of Microbiology and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 2 Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • 3 Gibco BioProduction Cell Culture and Cell Therapy, Thermo Fisher Scientific, 3175 Staley Road, Grand Island, NY 14072, USA.
  • 4 Department of Microbiology and Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: [email protected]
Type
Published Article
Journal
Cell Reports
Publisher
Elsevier
Publication Date
Apr 17, 2018
Volume
23
Issue
3
Pages
741–755
Identifiers
DOI: 10.1016/j.celrep.2018.03.084
PMID: 29669281
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

T cells compete with malignant cells for limited nutrients within the solid tumor microenvironment. We found that effector memory CD4 T cells respond distinctly from other T cell subsets to limiting glucose and can maintain high levels of interferon-γ (IFN-γ) production in a nutrient-poor environment. Unlike naive (TN) or central memory T (TCM) cells, effector memory T (TEM) cells fail to upregulate fatty acid synthesis, oxidative phosphorylation, and reductive glutaminolysis in limiting glucose. Interference of fatty acid synthesis in naive T cells dramatically upregulates IFN-γ, while increasing exogenous lipids in media inhibits production of IFN-γ by all subsets, suggesting that relative ratio of fatty acid metabolism to glycolysis is a direct predictor of T cell effector activity. Together, these data suggest that effector memory T cells are programmed to have limited ability to synthesize and metabolize fatty acids, which allows them to maintain T cell function in nutrient-depleted microenvironments. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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