T cell metabolic fitness in antitumor immunity

• Effector T cells and tumors utilize similar metabolic programs.
• Nutrient depletion and accumulation of waste products in tumors can limit T cells.
• Immunomodulatory signals can reduce T cell metabolic fitness.
• Blockade of PD-1 and CTLA4 can enhance T cell metabolism and function.

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.