STAT5 Signaling in Macrophages Regulates Mammary Gland Development and Tumorigenesis

Abstract

The studies performed in this dissertation have focused on the role of STAT5 signaling in macrophages during different environmental contexts. We have demonstrated that STAT5 controls macrophage function in the developing mammary gland by regulating aromatase expression and estrogen signaling. Using autochthonous and transplant models of mammary tumorigenesis, we have shown that STAT5 signaling regulates tumor-associated macrophage function by modulating the expression of immunoregulatory and co-stimulatory molecules. Finally, these studies have revealed the ability of a clinically-relevant JAK/STAT inhibitor to induce the expression of pro-tumorigenic factors in macrophages and have demonstrated the need to understand the effects of systemic therapies on other cells in the tumor microenvironment.