Figure 3.

The interactions among CAR-T cells, tumor cells and immunosuppressive tumor microenvironment. On the one hand, tumor cells and immunosuppressive cells in bone marrow microenvironment induce CAR-T cell exhaustion through direct cell-to-cell contact, such as PD-1/PDL-1 pathway and Fas/FasL pathway. Immunosuppressive cells could also release immune inhibitory cytokines such as IL-10 and TGF-β to impact the cytotoxicity of CAR-T cells and promote the generation of Treg cells. In addition, BMSCs could protect MM cells against CAR-T cells through the up-regulation of anti-apoptosis proteins in MM cells.