The role of STAT3 signaling in the tumor microenvironment. STAT3 signaling supports the communication between tumor cells and the tumor microenvironments. STAT3 drives immunosuppressive effects and tumor promoting effects by endothelial cells and fibroblasts. Activation of STAT3 in dendritic (DC) cells suppresses maturation, activation and antigen presentation which promotes immune tolerance. STAT3 activation in neutrophil, NK cells and effector T cells also has immunosuppressive effects. STAT3 signaling in macrophage favors M2-like polarization and increases PD-L1 expression while STAT3 activation proliferates MDSC population. STAT3 exerts immune tolerance in regulatory T (Treg) cells by enhancing CTLA4 expression and tumorigenesis in B cells by promoting survival, proliferation and development. STAT3 effect on endothelial cells to promote tumor vascularization. STAT3 in tumor associated fibroblast also enhance tumor metastasis. Collectively, STAT3 signaling is a key regulator of hallmark of cancers.