Figure 3.

STAT3 and STAT5-mediated crosstalks between melanoma and immune cells create an immunosuppressive network that propels metastatic progression. (A) STAT3-expressing tumors secrete factors that upregulate STAT3 in hematopoietic progenitor cells (HPCs). This results in the accumulation of Tregs and immature dendritic cells in the tumor microenvironment, which further inhibit the maturation of these cells. Due to the lack of mature dendritic cells, the tumor-attacking CD8+ T cells and NK cells cannot be stimulated. NK cells with inactive STAT3 can repress tumors, while STAT3 activation in NK cells blocks their tumor-lysing properties. (B) STAT5-activated NK cells are effective against melanoma cells. This property is suppressed by secretion of DKK2 from melanoma cells (see main text for details).