Abstract 5323: Distinct roles of IL-17A in inflammation-induced tumor development and tumor immunosurveillance

Abstract

Abstract While chronic inflammation is considered to be a critical component of tumorigenesis, the immune system can also prevent tumor development and/or growth. IL-17A and IL-17A secreting T cells, termed Th17 mediate inflammation via activation of a wide range of downstream inflammatory mediators that contribute to chronic inflammatory diseases. It also has been suggested that Th17 can be a constituent in tumor immunosurveillance since tumor-specific Th17 has been shown to eradicate established tumor. In the present study, we addressed the effects of inflammation/immunity driven by IL-17A on a primary tumor development model using a chemical carcinogen 3′-methylcholanthrene (MCA). We found that IL-17A deficient (IL-17A−/−) mice were protected from the primary tumor development by MCA. Paradoxically, the growth of primary tumors developed in IL-17A−/− mice was faster than that of tumors in WT (C57BL/6) mice. Although tumor cell lines derived from WT and IL-17A−/− mice grew equally in immunocompromised (T, B cell deficient C. B-17 scid) mice, those from IL-17−/− mice were easily rejected in C57BL/6 mice as compared to those from WT mice. Consistent with this, tumor growth of B16 melanoma, a non-immunogenic transplantable tumor cell line, was enhanced in IL-17A−/− mice. The apparently contrasting effects of IL-17A on tumor growth and development may reflect difference in cells producing IL-17A, namely cells mediate innate or acquired immunity. We transferred CD4+ T cells from WT mice into IL-17A−/−. While the transfer with CD4+ T cells from WT mice did not affect the primary tumor development in IL-17A−/− mice, the growth of primary tumors in IL-17A−/− mice transferred with WT CD4+ T cells was significantly suppressed. These results indicate that IL-17A promotes tumorigenesis possibly by enhancing inflammation and IL-17A produced by CD4+ T cells contributes to the immune surveillance to the emerging tumors as well. Overall, these results not only demonstrate that a single cytokine, IL-17A, plays contrasting role in tumor development and growth, but also indicate that immune inflammation-driven tumorigenesis and tumor immunosurveillance coexist in the same host. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5323.