Fig. 2

The actions between cancer cells and tumor microenvironment contribute to cancer immune escape. In tumor microenvironment, tumor cells secrete many kinds of chemokines and cytokines to inhibit the anti-tumor immune response by recruiting immunosuppressive cells. Specifically, tumor cells secrete CXCL15 and HMGB1 to recruit tumor-associated neutrophil (TAN) and secrete GM-CSF, CXCL1, VEGF and CXCL2 to recruit myeloid-derived suppressor cell (MDSC). MDSC act with T helper 17 cell (Th17) by IL-17, IL-6, IL-23 and TGF-β. Tumor cells secrete CCL5, CL22 and TNF to recruit regulatory T cell (Treg). Furthermore, tumor cells secrete VEGF, CSF1 and CCL2 to recruit tumor-associated macrophage (TAM). Treg cells further recruit TAM by secreting CCL22. In addition, tumor cells express and secrete responding proteins to interact with immune cells and inhibit their tumor-killing ability, as a result, promoting cancer immune escape. For example, overexpression of PD-L1 on tumor cells can interact with PD-1 expressed on T cells to deliver inhibitory signal. Meanwhile, tumor cells secrete extracellular vesicles, like exosomes which contains JAK/STAT3 pathway-related proteins, to surrounding tumor microenvironment. These proteins in tumor microenvironment interact with regulatory DC cell (DCreg), NK cells, Monocyte, and M1 macrophage to inhibit anti-tumor immune response and shape immunosuppressive microenvironment. As a result, immune escape happens in tumor cells