IL-17 promotes tumor development through the induction of tumor promoting microenvironments at tumor sites and myeloid-derived suppressor cells.

Abstract

The role of immune responses in tumor development is a central issue for tumor biology and immunology. IL-17 is an important cytokine for inflammatory and autoimmune diseases. Although IL-17-producing cells are detected in cancer patients and tumor-bearing mice, the role of IL-17 in tumor development is controversial, and mechanisms remain to be fully elucidated. In the current study, we found that the development of tumors was inhibited in IL-17R-deficient mice. A defect in IFN-gammaR increased tumor growth, whereas tumor growth was inhibited in mice that were deficient in both IL-17R and IFN-gammaR compared with wild-type animals. Further experiments showed that neutralization of IL-17 by Abs inhibited tumor growth in wild-type mice, whereas systemic administration of IL-17 promoted tumor growth. The IL-17R deficiency increased CD8 T cell infiltration, whereas it reduced the infiltration of myeloid-derived suppressor cells (MDSCs) in tumors. In contrast, administration of IL-17 inhibited CD8 T cell infiltration and increased MDSCs in tumors. Further analysis indicated that IL-17 was required for the development and tumor-promoting activity of MDSCs in tumor-bearing mice. These data demonstrate that IL-17-mediated responses promote tumor development through the induction of tumor-promoting microenvironments at tumor sites. IL-17-mediated regulation of MDSCs is a primary mechanism for its tumor-promoting effects. The study provides novel insights into the role of IL-17 in tumor development and has major implications for targeting IL-17 in treatment of tumors.

• Authors: Donggou He, Hui Li, Nabiha Yusuf, Craig A Elmets, Jun Li, John D Mountz, Hui Xu
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 184 Issue 5 Pg. 2281-8 (Mar 01 2010) ISSN: 1550-6606 [Electronic] United States
• PMID: 20118280 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antibodies
• Interleukin-17
• Receptors, Interferon
• Receptors, Interleukin-17
• interferon gamma receptor

Topics

• Animals
• Antibodies (immunology, pharmacology)
• Apoptosis (immunology)
• CD8-Positive T-Lymphocytes (immunology, pathology)
• Cell Line, Tumor
• Flow Cytometry
• In Situ Nick-End Labeling
• Interleukin-17 (immunology, pharmacology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myeloid Cells (immunology, pathology)
• Neoplasms, Experimental (genetics, immunology, pathology)
• Receptors, Interferon (deficiency, genetics, immunology)
• Receptors, Interleukin-17 (deficiency, genetics, immunology)
• Tumor Burden (drug effects, immunology)