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

Author(s)

Benevides, Luciana ^[1] ; da Fonseca, Denise Morais ^[1] ; Donate, Paula Barbim ^[1] ; Tiezzi, Daniel Guimaraes ^[2] ; De Carvalho, Daniel D. ^{[3, 4]} ; de Andrade, Jurandyr M. ^[2] ; Martins, Gislaine A. ^{[5, 6]} ; Silva, Joao S. ^[1]

Affiliation

^[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, BR-14049900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Gynecol & Obstet, Breast Dis Div, BR-14049900 Sao Paulo - Brazil

^[3] Univ Toronto, Dept Med Biophys, Toronto, ON - Canada

^[4] Univ Toronto, Ontario Canc Inst, Princess Margaret Canc Ctr, Univ Hlth Network, Toronto, ON M5S 1A1 - Canada

^[5] Cedars Sinai Med Ctr, F Widjaja Fdn Inflammatory Bowel & Immunobiol Res, Los Angeles, CA 90048 - USA

^[6] Cedars Sinai Med Ctr, Dept Med & Biomed Sci, Los Angeles, CA 90048 - USA

• Document type: Journal article
• Source: Cancer Research; v. 75, n. 18, p. 3788-3799, SEP 15 2015.
• Web of Science Citations: 50

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 TNF alpha, 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. (C) 2015 AACR. (AU)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 12/08240-8 - Role of Blimp-1 in differentiation and function of Th9 cells.
• Grantee: Luciana Benevides
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 12/14524-9 - Modulation of T lymphocytes differentiation in infections by Protozoa, Fungi and Bacteria
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants