Enrichment of regulatory T cells in invasive breast tumor correlates with the upregulation of IL-17A expression and invasiveness of the tumor

Author(s)

Benevides, Luciana ^[1] ; Cardoso, Cristina R. B. ^[2] ; Tiezzi, Daniel G. ; Marana, Heitor R. C. ^[3] ; Andrade, Jurandyr M. ^[3] ; Silva, Joao S. ^[1]

Affiliation

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

^[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, BR-14049900 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Gynecol & Obstet, Sch Med Ribeirao Preto, Breast Dis Div, BR-14049900 Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: European Journal of Immunology; v. 43, n. 6, p. 1518-1528, JUN 2013.
• Web of Science Citations: 51

Abstract

Breast cancer is a leading cause of neoplasia-associated death in women worldwide. Regulatory T (Treg) and Th17 cells are enriched within some tumors, but the role these cells play in invasive ductal carcinoma (IDC) of the breast is unknown. We show that CD25(+)CD4(+) T cells from PBMCs and tumor express high levels of Foxp3, GITR, CTLA-4, and CD103, indicating that tumor-infiltrating Treg cells are functional and possibly recruited by CCL22. Additionally, we observed upregulation of Th17-related molecules (IL-17A, RORC, and CCR6) and IL-17A produced by tumor-infiltrating CD4(+) and CD8(+) T lymphocytes. The angiogenic factors CXCL8, MMP-2, MMP-9, and vascular endothelial growth factor detected within the tumor are possibly induced by IL-17 and indicative of poor disease prognosis. Treg and Th17 cells were synchronically increased in IDC patients, with positive correlation between Foxp3, IL-17A, and RORC expression, and associated with tumor aggressiveness. Therefore, Treg and Th17 cells can affect disease progression by Treg-cell-mediated suppression of the effector T-cell response, as indicated by a decrease in the proliferation of T cells isolated from PBMCs of IDC patients and induction of angiogenic factors by IL-17-producing Th17. The understanding of regulation of the Treg/Th17 axis may result in novel perspectives for the control of invasive tumors. (AU)

• FAPESP's process: 07/53940-0 - The regulatory T cells and TH17 in the immune response against infections, tumors and autoimmune diseases
• Grantee: João Santana da Silva
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 08/04606-2 - CD4+CD25+ T regulatory and Th17 cells in immunity to breast tumour
• Grantee: Luciana Benevides
• Support Opportunities: Scholarships in Brazil - Doctorate