Targeting Metabolism to Improve CAR-T Cell Immunotherapy

The transfer of genetically-engineered chimeric antigen receptor (CAR)-T cells has recently become one of the most promising approaches in the treatment of cancer. Like normal T cells, CAR-T cells are dependent on an adequate supply of nutrients and energy to be able to proliferate and mediate anti-tumor responses. However, CAR-T cell proliferation and cytotoxicity are limited by the elevated metabolic demands of actively dividing cancer cells, which deplete nutrients from the tumor microenvironment (TME). Thus, a variety of TME-imposed metabolic “barriers” must be overcome by artificially altering the metabolism of CAR-T cells to increase their clinical performance, especially in solid tumors. In this review, we summarize the metabolic interactions between T cells and the TME, discuss the metabolic reprogramming of T cells, present recent progress in the application of metabolic interventions in CAR-T cell therapy, and finally allude to future directions in this field.