IL17A critically shapes the transcriptional program of fibroblasts in pancreatic cancer and switches on their protumorigenic functions
Gianluca Mucciolo, Claudia Curcio, Cecilia Roux, Wanda Y. Li, Michela Capello, Roberta Curto, Roberto Chiarle, Daniele Giordano, Maria Antonietta Satolli, Rita T. Lawlor, Aldo Scarpa, Pavol Lukáč, Dmitry Stakheev, Paolo Provero, Luca Vannucci, Tak W. Mak, Francesco Novelli, Paola Cappello
Abstract
Significance There are controversial data about the protumoral role of pancreatic cancer stroma, and dissecting multiple aspects will help to develop effective tailored therapies. Interleukin-17A (IL17A) has been reported to accelerate pancreatic acinar–ductal metaplasia, be important for maintaining stem-like cancer cells, and recruit immunosuppressive granulocytes into the tumor. Here we unveil a relationship between IL17A and pancreatic stromal cells, which strongly modifies their gene and protein expression profiles. Ablation of IL17A, in fact, modifies the cytokines/factors released by tumor fibroblasts by limiting T cell immunosuppression. IL17A inhibition may represent an important tool for designing novel combined therapeutic approaches.