IL-17 promotes mammary tumor progression by changing the behavior of tumor cells and eliciting tumorigenic neutrophils recruitment

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL-17 levels. Studying the role of IL-17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL-17, whereas IL-17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF and TNF
, and their depletion suppressed tumor growth. IL-17A also induced IL-6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL-17A changed the gene expression profile and the behavior of non-metastatic tumor cells, causing tumor growth in vivo, confirming the pro-tumor role of IL-17. Furthermore, high IL-17 expression was associated with lower disease-free survival (DFS) and worse prognosis in IDC patients. Thus, IL-17 blockade represents an attractive approach for the control of invasive breast tumors.