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Emerging concepts of T cell metabolism as a target of immunotherapy

Abstract

T cells have a pivotal protective role in defense against infection and cancer but also are instrumental in the development of many autoimmune diseases. The regulation of nutrient uptake and utilization in T cells is critically important for the control of their differentiation, and manipulating metabolic pathways in these cells can alter their function and longevity. While the importance of T cell metabolic remodeling in different physiological settings is not fully understood, there is a growing realization that inappropriate metabolic remodeling underlies many aberrant immune responses and that manipulating cellular metabolism can beneficially enhance or temper immunity. Here we comment on the basic metabolic pathways in T cells, followed by a discussion on up-to-date findings about the relationship between metabolism and T cell function and longevity. Furthermore, we expand on potential approaches and applications in which T cells might be manipulated by the reprogramming of metabolic pathways for therapeutic purposes.

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Figure 1: Basic metabolic pathways in a T cell.

Kim Caesar/Nature Publishing Group

Figure 2: Metabolic interplay in the local microenvironment.

Kim Caesar/Nature Publishing Group

Figure 3: Targeting T cell metabolism for therapy.

Kim Caesar/Nature Publishing Group

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Acknowledgements

Supported by the US National Institutes of Health (R01CA181125) and the Burroughs Wellcome Fund.

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Correspondence to Chih-Hao Chang or Erika L Pearce.

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Chang, CH., Pearce, E. Emerging concepts of T cell metabolism as a target of immunotherapy. Nat Immunol 17, 364–368 (2016). https://doi.org/10.1038/ni.3415

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  • DOI: https://doi.org/10.1038/ni.3415

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