SRP186490 PRJNA523593 GSE126879 Suppressive function of MDSC is under bidirectional control of intrinsic and immunotherapy-induced type I IFN in pancreatic cancer Tumors entertain a highly immunosuppressive network by merging features of regulatory cytokines and cell populations to evade immune control. Myeloid-derived suppressor cells (MDSC) comprise populations of immature myeloid cells in tumor-bearing hosts with a highly immunosuppressive capacity. We could previously identify RIG-I-like helicases (RLH) as targets for the immunotherapy of pancreatic cancer inducing immunogenic tumor cell death and type I interferons (IFN), as key mediators linking innate with adaptive immunity. Here, we show that autochthonous type I IFN signaling is critical for MDSC to gain suppressive function. In contrast, RNA sequencing of MDSC from RLH-ligand-treated mice showed an IFN-driven gene signature and a switch from a M2/G2- towards a M1/G1-polarized phenotype. Functional assays confirmed the loss of the T cell suppressive capacity. Our study identifies a dual role of type I IFN signaling in MDSC´s suppressive function, and RLH-mediated tumor control. Overall design: T110299 pancreatic cancer cells, that derived from a genetically engineered spontaneous pancreatic cancer mouse (Ptf1a-Cre LSL-KrasG12DLSL-Trp53fl/R172H), were implanted orthotopically in eight C57BL6 mice. Four Mice were treated twice with poly(I:C)-PEI and four mice were treated with glucose as a control. PMN-MDSC as well as M-MDSC were isolated from tumor and spleen. Whole transcriptome of isolated MDSC was then analyzed by RNA sequencing. GSE126879 pubmed 31694706