Figure 1. Balanced activation and opposite effects of STAT1 and STAT3 in tumor settings. Prevalent STAT3 activation and/or expression, often downstream of IL-6 production, favors tumor development and maintenance. Tumor cell proliferation and survival are favored not only directly, but also indirectly by the maintenance of cancer stem cells and the switch to aerobic glycolysis. STAT3-dependent tumor-produced soluble factors such as IL-10 and VEGF induce STAT3-dependent tolerance in the immune cells. Moreover, STAT3 activation enhances metastasis formation by inducing EMT and cell migration and by increasing tumor angiogenesis. In contrast, the prevalence of STAT1 activation is fundamental to directly and indirectly block cell cycle progression and induce apoptosis of cancer cells. STAT1 elicits an efficient anti-tumor immune response both by stimulating antigen presentation to the immune system and by stimulating immune cells activity. CSCs, cancer stem cells; DC, dendritic cells; EMT, epithelial to mesenchymal transition (modified from ref. 2).