title: T cell metabolic fitness in antitumor immunity.
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.
authors.affiliation: Department of Pharmacology and Cancer Biology, Department of Immunology, Duke Molecular Physiology Institute, Duke University, Durham, NC 27710, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Siska
authors.affiliation: 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.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Rathmell
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007109:Immunity / Q000276:immunology*; D009369:Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents
keywords: CTLA4; IDO; PD-1; T cell metabolism; antitumor immunity; checkpoint blockade; glycolysis; tumor microenvironment