The Accumulation of IL17-Expressing cells Associated with Tumor Progression in HNC

Background: Interleukin 17 (IL-17) is a pro-inflammatory cytokine, is known to affect both the development of autoimmune diseases and cancers. However, the role of IL-17 in cancer development remains controversial. The presence of IL-17 appeared to suppress tumor growth and metastasis by enhancing cytotoxic T-cell responses. In contrast, IL-17 could promote tumor progression through enhancing angiogenesis or inducing myeloid derived suppressor cell infiltration, leading to the suppression of anti-tumor immunity. Here we have demonstrated the contribution of IL-17 in the development of head and neck cancer (HNC) via investigating the direct effects of IL-17 on HNC cells, the accumulation of IL-17⁺ T cells as well as their related cytokine production. Also, the impact is revealed by correlating such findings with the clinical data of HNC. Methods: Peripheral blood samples were obtained from the OPD patients of HNC in Chang Gung Memorial Hospital, and multi-color flow cytometric analysis and enzyme conjugated immunoassays were utilized to identify the IL-17 producing T cell subsets and the production of inflammation-associated cytokines including VEGF. Head and neck cancer cell lines were treated with exogenous IL-17 and analyzed for cell growth as well as gene expression by real-time RT-PCR. Results: A significant accumulation of IL-17 producing T cells was found in HNC patients and their frequencies were correlated with disease stages and the patients' peripheral blood mononuclear cells secreted higher amount of IL-17 along with other related factors including VEGF. Meanwhile, the addition of IL-17 appeared to induce OECM-1 and SAS cells to secret more VEGF and to promote its cell growth. In addition, HNC patients at later stages showed to have higher frequencies of IL-17 expressing cells. Also, the survival rate of patients in the same category decreased in those harboring higher percentages of IL-17 expressing T cells. Conclusion: These findings suggest that both IL-17 and IL-17 related responses are directly associated with tumor development and progression of HNC.