Figure 5.

Constitutive Stat3 activity in tumors affects the surrounding microenvironment. Chronic Stat3 activation in tumor cells results in secretion of IL-1β, IL-6, and IL-10; these in turn act on nontumor cells, T helper 17 cells (Th17) and tumor associated macrophages (TAM) resulting in further secretion of cytokines, which act in a feedback loop to promote growth and differentiation of the tumor cells. Stat3-directed secretion of IL-10 by the tumor cells also results in inhibition of antitumor immunity, for example by inhibiting the maturation of dendritic cells (DCs). Thus, Stat3 and the cytokines that it induces, promote tumor invasion and metastasis. Diagram adapted from Pensa et al. (2009).