CAR T cell therapy and the tumor microenvironment: Current challenges and opportunities

Chimeric antigen receptor (CAR) T cell therapy has demonstrated remarkable outcomes in individuals with hematological malignancies, but its success has been hindered by barriers intrinsic to the tumor microenvironment (TME), particularly for solid tumors, where it has yet to make its mark. In this article, we provide an updated review and future perspectives on features of the TME that represent barriers to CART cell therapy efficacy, including competition for metabolic fuels, physical barriers to infiltration, and immunosuppressive factors. We then discuss novel and promising strategies to overcome these obstacles that are in preclinical development or under clinical investigation. [Display omitted] The success of chimeric antigen receptor (CAR) T cell therapy has been hindered by barriers intrinsic to the tumor microenvironment, including metabolic fuel competition, physical barriers to effective CAR T cell infiltration, and immunosuppressive cytokines and cell types. We review novel strategies and sophisticated CAR designs that may overcome these barriers.