title: 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.affiliation: Department of Dermatology, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: Donggou
authors.initials: D
authors.lastname: He
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Nabiha
authors.initials: N
authors.lastname: Yusuf
authors.forename: Craig A
authors.initials: CA
authors.lastname: Elmets
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D020381:Interleukin-17 / Q000276:immunology* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D017471:Receptors, Interferon / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D053722:Receptors, Interleukin-17 / Q000172:deficiency / Q000235:genetics / Q000276:immunology; D047368:Tumor Burden / Q000187:drug effects / Q000276:immunology; D000096743:Interferon gamma Receptor
chemical_list: D000906:Antibodies; D020381:Interleukin-17; D017471:Receptors, Interferon; D053722:Receptors, Interleukin-17; D000096743:Interferon gamma Receptor