Figure 6.

The TME is primarily composed of tumor cells, immune cells, immunosuppressive cells (including TAM, MDSC and Treg) and cytokines, CAFs, ECM and dysregulated tumor vasculatures. On the one hand, ECM produced by CAFs forms a physical barrier, impairing the infiltration of the CAR-T cells. On the other hand, the soluble cytokines secreted by the CAFs mediate immuno-suppressive responses, and consequently, facilitate the survival of tumor cells. The hypoxic and acidic environment directly deteriorate the metabolism of T cells while activating suppressive Tregs, leading to immunosuppression of CAR-T cells.