Th17 Cells In Tumor Microenvironment Research Articles

Abstract A120: The infiltration of Th17 cells in tumor microenvironment negatively correlate with the prognosis of the patients with head and neck squamous cell carcinoma

Abstract Introduction: Head and Neck squamous cell carcinoma (HNSCC) remains to the malignancies with the unsure prognosis. Regarding the etiology, we are facing different clinical manifestation, behavior and overall survival. This fact can be explained by the differences in the immune response of the patients. Understanding of the basic principles of the immune system of HNSCC patients would help us to better combine the therapeutical strategies with the respect to the immune cell subpopulations and their regulation. One of the most important cells are Th17 lymphocytes, which are increased in the peripheral blood and the microenvironment of many types of cancers. Methods: 178 patients with primary HNSCC were included to the study. Samples of the peripheral blood and from the primary tumors, metastatic lymph nodes and non-affected lymph nodes were collected at the moment of surgical therapy and measured by flow cytometry. The data were analyzed by the Cox regression and compared with the group of healthy blood donors. Sixty six tumors out of 178 primary tumors were localized in the tonsillar region, 50 in the root of the tongue, 33 in the larynx and 8 in hypopharynx. The average follow-up was 40 months. Results: For the prognosis of the patients the most important oncological parameters were T and N stadium of the disease (p = 0.02, resp. p = 0.03), radicality of the surgery (p = 0.006), presence of the adverse prognostic risk factors (p = 0.01). From the analyzed parameters of the immune system we found negative prognostic correlation of the level of B lymphocytes (CD19+; p = 0.03) and the positive prognostic correlation of the level of naïve CD4+ T cells (CD4+CD45RA+, p = 0.02) in the peripheral blood of the patients. We found strong negative prognostic correlation of the Th17 cells (CD4+CD161+) in the peripheral blood (p = 0.04) and also in the tumor microenvironment (p = 0.005). Conclusion: We can conclude that the examination of parameters of immune system could be helpful for better understanding of biological behavior and interaction of the HNSCC. The level of Th17 cells in both periphery and in the tumor microenvironment correlate with the worst survival of the patients with the HNSCC. The analyses of the Th17 level in the peripheral blood before the therapy could help us with the prediction of the cause of the disease. The future studies should be focused on the changes in immune cells infiltration in response to the different therapeutical strategies in HNSCC oncology. Acknowledgments: The research was supported by AZV MZ CR (grant No. NV16-28594A and NV16-28600A). Note: This abstract was not presented at the conference. Citation Format: Jan Boucek, Michal Zabrodsky. The infiltration of Th17 cells in tumor microenvironment negatively correlate with the prognosis of the patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr A120.

Pro-Tumor and Anti-Tumor Functions of IL-17 and of TH17 Cells in Tumor Microenvironment

Summary The current review reveals the seven subclasses of CD4+ T helper cells, i.e. Th1, Th2, Th9, Th17, Th22, regulatory T cells and Tfh, the cytokines produced by them and their role in tumor microenvironment. Main attention was paid to IL-17 and Th17 cells. IL-17-producing cells were described, among which were Treg17 cells and Tc17 cells. The transcription factors, engaged in the activation of Th17 cell differentiation were reviewed. It was shown that Th17 cells might possess regulatory functions in tumor microenvironments that directs toward immunosuppression. The reciprocity between Treg and Th17 cells is realized when the production of a large amount of TGF-β in tumors causes Treg cell differentiation, and the addition of IL-6 shifts the differentiation of naïve T cells to Th17 cells. The main pro-tumor role of IL-17 is the promotion of tumor angiogenesis through stimulation of fibroblasts and endothelial cells. The antitumor functions of IL-17 are associated with enhancement of cytotoxic activity of tumor specific CTL cells and with angiogenesis that provide channels through which immune cells might invade tumor and promote antitumor immunity.