Fig. 2

Tumor cells which orchestrate an immune inhibitory microenvironment compromise the activity of CAR T cells. Tumor cells, immunosuppressive cells (e.g., myeloid derived suppressor cells and regulatory T cells) and tumor-associated stroma cells inhibit the activity of CAR T cells by expression of inhibitory molecules (e.g., PDL1) and release of inhibitory cytokines such as IL-10, indoleamine 2,3-dioxygenase (IDO), transforming growth factor-β (TGF-β), arginase and IL-4. In this immunosuppressive microenvironment, tumor infiltrating CAR T cells rapidly lose their cytolytic and cytokine secretion capacity, and tend to be exhaustion. Approaches targeting suppressive factors can improve the efficacy of CAR T cells