Fig. 2

STAT3 regulates immunosuppression and the crosstalk between tumor cells and immune cells in TME. Left panel, STAT3 activation induces the immunosuppression of innate immune, adaptive immune cells, as well as tumor-promoting activities of fibroblasts and endothelial cells. STAT3 activation promotes the expansion and proliferation of immunosuppressive MDSC and B cells, and drives the expansion and pro-tumor M2 polarization of immunosuppressive Treg cells and macrophage cells. Moreover, STAT3 activation simultaneously induces the expression of immune checkpoint molecules including PD-1, TIGIT and CTLA-4 in these cells. In addition, STAT3 activation impairs the immune-associated antitumor activities of neutrophils, CD8⁺ T cells and NK cells. STAT3 activation also suppresses the antitumor activity of dendritic cells via disrupting the maturation and antigen presentation. Purple fonts represent the innate immune cell subsets, orange fonts represent adaptive immune cell subsets. Red arrows represent tumor promoting function and blue arrows represent the decreasing antitumor function. Right panel, STAT3 regulates the crosstalk between tumor cells and immune cells in TME. Increasing STAT3 activities in tumor cells promotes the production of IL-6, IL-10, VEGF, TGFβ. STAT3 activation and these cytokines and factors mediated the expansion and polarization of MDSC and M2 macrophage. The increasing STAT3 activities diminish the maturation of dendritic cells which leads to the accumulation of Treg cells and thus blocks the antitumor activities of CD8⁺ T and NK cells. Created with BioRender.com