IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment

Abstract

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 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 TNFa, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors. Cancer Res; 75(18); 3788-99. Ó2015 AACR.

Interleukin-17–Producing Neutrophils Link Inflammatory Stimuli to Disease Progression by Promoting Angiogenesis in Gastric Cancer

“…Elevated IL17 expression has also been observed in patients with corneal ulcers caused by filamentous fungi; neutrophils are the predominant infiltrating cells in these ulcers (19)(20)(21). Although IL17 has been detected in several human tumors (22), its cellular sources remain unclear. Gastric cancer is the fourth most common human malignant disease and the second leading cause of cancer-related death worldwide (23).…”

Role of poly(ε-caprolactone) lipid-core nanocapsules on melanoma–neutrophil crosstalk

“…2 Neutrophils are recruited from the blood mainly responding to chemotactic agents secreted by surrounding or tumor cells, such as chemokine CXCL12, interleukin (IL)-17 and vascular endothelial growth factor (VEGF). [14][15][16][17] In the tumor microenvironment, tumor-associated neutrophils (TANs) switch to phenotype differentiation, ie, anti-tumorigenic (N1) or pro-tumorigenic (N2). The differentiation is driven by type 1 interferon γ (IFNγ) and transforming growth factor-β (TGF-β), which polarize to N1 and N2 phenotype, respectively.…”

Analysis of Immune Cells from Human Mammary Ductal Epithelial Organoids Reveals Vδ2+ T Cells That Efficiently Target Breast Carcinoma Cells in the Presence of Bisphosphonate

“…Whereas γδ T cells typically have a T helper 1 (T H1 ) cytokine production phenotype that is characterized by the production of high levels of IFN-γ, it has recently become clear that lymphoid cells in and around epithelial tissues are also responsible for the production of interleukin (IL-) 17, a cytokine that promotes epithelial integrity but that may also play a pathogenic role in tumorigenesis (32). Therefore, we tested cytokine production by primary T cells in organoid preparations by stimulating them with PMA and ionomycin, then performing intracellular cytokine staining for IFN-γ and IL-17.…”