Targeting the immune-suppressive tumor microenvironment to potentiate CAR T cell therapy

Chimeric antigen receptor (CAR) T cell therapy is a promising new immunotherapy that reprograms patient T lymphocytes to specifically recognize and kill tumor cells. CAR T cell therapy has produced some dramatic responses in acute lymphoblastic leukemia and lymphomas, but responses have been less spectacular in solid tumors. To make CAR T cell therapy effective for solid tumors, CAR T cells must overcome an immune-suppressive tumor microenvironment (TME) that attenuates CAR T cell function. This review provides insights into mechanisms of CAR T cell therapy resistance with respect to the TME and offers strategies for improving CAR T cell therapy by targeting immune-suppressive factors in tumors.