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Trends Immunol. 2015 Apr;36(4):257-64. doi: 10.1016/j.it.2015.02.007. Epub 2015 Mar 12.

T cell metabolic fitness in antitumor immunity.

Author information

1
Department of Pharmacology and Cancer Biology, Department of Immunology, Duke Molecular Physiology Institute, Duke University, Durham, NC 27710, USA.
2
Department of Pharmacology and Cancer Biology, Department of Immunology, Duke Molecular Physiology Institute, Duke University, Durham, NC 27710, USA. Electronic address: Jeff.rathmell@duke.edu.

Abstract

T cell metabolism has a central role in supporting and shaping immune responses and may have a key role in antitumor immunity. T cell metabolism is normally held under tight regulation in an immune response of glycolysis to promote effector T cell expansion and function. However, tumors may deplete nutrients, generate toxic products, or stimulate conserved negative feedback mechanisms, such as through Programmed Cell Death 1 (PD-1), to impair effector T cell nutrient uptake and metabolic fitness. In addition, regulatory T cells are favored in low glucose conditions and may inhibit antitumor immune responses. Here, we review how the tumor microenvironment modifies metabolic and functional pathways in T cells and how these changes may uncover new targets and challenges for cancer immunotherapy and treatment.

KEYWORDS:

CTLA4; IDO; PD-1; T cell metabolism; antitumor immunity; checkpoint blockade; glycolysis; tumor microenvironment

PMID:
25773310
PMCID:
PMC4393792
DOI:
10.1016/j.it.2015.02.007
[Indexed for MEDLINE]
Free PMC Article

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