Reprogramming lipid metabolism prevents effector T cell senescence and enhances tumor immunotherapy.

ABSTRACT: The functional state of T cells is a key determinant for effective antitumor immunity and immunotherapy. Cellular metabolism, including lipid metabolism, controls T cell differentiation, survival, and effector functions. Here, we report that development of T cell senescence driven by both malignant tumor cells and regulatory T cells is a general feature in cancers. Senescent T cells have active glucose metabolism but exhibit unbalanced lipid metabolism. This unbalanced lipid metabolism results in changes of expression of lipid metabolic enzymes, which, in turn, alters lipid species and accumulation of lipid droplets in T cells. Tumor cells and T_reg cells drove elevated expression of group IVA phospholipase A₂, which, in turn, was responsible for the altered lipid meta

SUBMITTER: Liu X 

PROVIDER: S-EPMC12040281 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature