Il17 Favours Carcinogenesis And Limits The Anti-Tumor Responses In Pancreatic Cancer

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PAPancreatic ductal adenocarcinoma (PDA) is a fatal medical condition with few advances in therapy and patient survival. The role of IL17 and Th17 in cancer progression and anti-tumor immunity is still controversial. In this study we have investigated the role of IL17 and Th17 in PDA carcinogenesis and anti-tumor responses.IL-17 production and Th17 percentage in blood from PDA patients and control subjects as well from genetically engineered mice (GEM) that spontaneously develop PDA, were analysed by ELISA and FACS respectively. Survival of GEM mice crossed with IL-17 KO mice (GEM/IL17KO) was analysed by Kaplan-Meier analysis. WT or IL17KO mice that were prophylactically vaccinated with a plasmid coding for the PDA-associated antigen α-enolase (ENO1) (1-3), were subsequently injected with PDA cell line derived from GEM. Tumor growth and the induction of an antigen-specific immune response were monitored.We have found a statistically significant increase of peripheral Th17 cells and a decrease of Th1 in PDA patients compared to healthy subjects. GEM mice showed 3-fold more RORγT+ cells at the onset of duct transformation, which dropped to the level of control mice at 20 weeks and lasted until 35 weeks. Notably, GEM/IL17 KO mice survived significantly more than GEM mice, even if there were no changes in the tumor onset. In addition, in GEM/IL17 KO mice, we observed an increased fibrotic reaction compared to GEM mice starting from early stage of disease. Lastly, ENO-1 DNA vaccination in IL17KO mice significantly decreased PDA cells growth and enhanced the CD8 T cell response compared to that observed in WT mice.Our data suggest that the absence of IL17 does not affect the tumor onset but the progression, likely affecting the immune response, which seems to be able to better counteract tumor growth in the absence of this cytokine.Tomaino et al., J Proteome Res. 2007;6:4025-31; Cappello et al, Int. J. Cancer. 2009;125:639-48; Cappello P et al, Gastroenterology. 2013;144:1098-106.Citation Format: Paola Cappello, Roberta Curto, Gianluca Mucciolo, Simona Rolla, Elisabetta Tonoli, Francesco Novelli. IL17 favours carcinogenesis and limits the anti-tumor responses in pancreatic cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3170. doi:10.1158/1538-7445.AM2015-3170