Abstract 4738: IL-17 induces myeloid-related stimulating factors by stromal cells

Pancreatic ductal adenocarcinoma (PDA) is one of the most aggressive cancer with a 5-year survival rate of ∼ 8%. An hallmark of PDA is the massive desmoplasia and the complex stromal-tumor interaction, regulated by a pletory of secreted factors. The role of IL-17 and T-helper 17 in cancer progression or anti-tumour immunity remain controversial. To assess the role of this molecule, we crossed genetically engineered mice (GEM) characterized by a spontaneous PDA development, with IL-17 knockout mice (GEM/IL-17 KO). The absence of IL-17 correlated with an increased pancreatic fibrosis, evaluated by second harmonic generation approach. The transcripts and secretome of Cancer Associated Fibroblasts (CAFs), obtained from tumors arose in both WT and IL-17 KO GEM, have been evaluated. More than 60 genes were differently modulated in the CAFs from GEM/IL-17 KO mice. Among them, GM-CSF, G-CSF, M-CSF, CXCL1 and 2 where strongly up-regulated in GEM/WT compared to GEM/IL-17 KO mice and significantly inhibited by the addition of the recombinant cytokine. The absence of those factors paralleled an increased Th1-skewed cytokine pattern released by CAF that affected T cell infiltration and response. Taken together, these results suggest that IL-17 does affect the tumor progression by promoting a CAFs-mediated release of cytokines involved in myeloid cells recruitment and suppression of an anti-tumoral immune response. This feature defines IL-17 as a potential target to shape the tumor microenvironment and favour immunotherapy success. Citation Format: Gianluca Mucciolo, Roberta Curto, Claudia Curcio, Cecilia Roux, Luca Vannucci, Francesco Novelli, Paola Cappello. IL-17 induces myeloid-related stimulating factors by stromal cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4738.