This comprehensive review by Kishton et al. covers the metabolic activity of T cells as it relates to longevity, differentiation trajectory and end state, functionality, and anti-tumor activity. It also explores the metabolic competition T cells face from other cells in the tumor microenvironment and suggests possible metabolic interventions to counter the dampening of antitumor immune responses.
Cancer immunotherapy is an increasingly successful strategy for the treatment of patients who have advanced or conventional therapy-resistant cancers. T cells are key mediators of tumor destruction and their specificity for tumor-expressed antigens is of paramount importance, but other T cell-intrinsic qualities, such as durability, longevity, and functionality also play important roles in determining the efficacy of immunotherapy. The cellular energetic pathways that are utilized by T cells play a key role in regulating each of these qualities. Metabolic activity, which both regulates and is regulated by cellular signaling pathways and epigenetics, also profoundly influences the trajectories of T cell differentiation and fate. In this Review, we discuss how cell metabolism influences T cell anti-tumor activity, the metabolic qualities of highly-functional T cells, and strategies to modulate metabolism for improving the immune response to tumors.