The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL-17 levels. In this study, we investigated the role of IL-17 in invasive breast tumor pathogenesis. We found that metastatic 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, and their depletion suppressed tumor growth. Moreover, IL-17 induced IL-6 and CXCL1 production in tumor cells, and IL-6 depletion reduced metastatic tumor growth and infiltration by Th17 cells and neutrophils. In addition, inoculation of a non-metastatic mammary tumor cell line pre-incubated with IL-17 promoted tumor growth, 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.

Biopsies of patients with breast tumors