Figure 4.

TEXs have various immunosuppressive functions. Cancer cells release tumor-derived exosomes (TEXs). TEXs suppress the activities of T-cells and natural killer (NK) cells. Exosomal PD-L1 (programmed death-ligand 1) suppresses T-cell activity by binding to PD-1 (programmed cell death protein 1) on T-cells. TEXs activate myeloid-derived suppressor cells (MDSCs), regulatory T-cells, and neutrophils in a pro-tumor manner. TEXs invade tumor-draining lymph nodes and disrupt SCS cells, which form the protective outer layer of the lymph nodes; then access B-cell zone to activate B-cells in a tumor-supportive manner. Next, TEXs leak into the blood stream and eventually develop the metastatic niche. In the metastatic sites, TEXs are uptaken by tissue resident epithelial cells and macrophages, which in turn release inflammatory cytokines. These cytokines cause MDSCs to migrate to the metastatic niche and hence make it more tumor-friendly.