T cell metabolic fitness in antitumor immunity

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


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / immunology
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Immunity / immunology*
  • Neoplasms / drug therapy*
  • Neoplasms / immunology*
  • Neoplasms / pathology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology


  • Antineoplastic Agents