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 MDSCs suppressive function, and RLH-mediated tumor control. SOURCE: Caroline Friedel Ludwig-Maximilians-Universität München

Pluto Bioinformatics

GSE126879: Suppressive function of MDSC is under bidirectional control of intrinsic and immunotherapy-induced type I IFN in pancreatic cancer