P08.56 Autocrine activation of the IFN signaling pathway modulates the immunogenicity of glioma cells

Abstract

Introduction: Interferons (IFN) are cytokines that are typically induced upon viral infection, but can be constitutively expressed also in the absence of acute infection to regulate various processes. Alterations in IFN signaling have been observed in numerous malignancies, however the physiological role of autocrine and paracrine IFN signaling remains poorly understood. Methods: Here, we aimed at characterizing autocrine IFN-β signaling and its functional impact in glioma cells in vitro using RNA interference-mediated gene silencing. Results: Exposure to recombinant IFN-β led to the induction of the classical IFN-response gene Myxovirus A (MxA) in a panel of glioma cell lines, whereas some glioma-initiating cells showed basal MxA protein expression even in the absence of exogenous IFN-β, indicating the presence of constitutive IFN signaling. Silencing of the type I IFN receptors IFNAR1 or IFNAR2, or the ligands IFN-α or IFN-β, decreased MxA levels, providing evidence for the existence of an autocrine type I IFN signaling loop. On a functional level, we observed reduced PD-L1, MHC class I and class II expression and increased susceptibility to NKL cell-mediated lysis upon IFNAR silencing, suggesting that constitutive IFN signaling in glioma cells plays an immunomodulatory role. Conclusion: Our findings point to an important role of constitutive IFN signaling in the immune evasion of glioma cells.