Abstract P047: Inactivation of IFN signaling drive immunosuppressive MDSC function and can be therapeutically targeted

Abstract Myeloid-derived suppressor cells (MDSC) are pathologically activated neutrophils and monocytes with potent immune suppressive activity that promote tumor progression and impair the efficacy of anti-tumor therapeutics. Herein we show that type I interferons (IFN1) receptor dampen immune suppressive activity of MDSC. Downregulation of the IFNAR1 is found in MDSC from cancer patients and mouse tumor models. Downregulation of IFNAR1 depends on the activation of the p38 protein kinase and is required for activation of the immune suppressive phenotype moreover genetic stabilization of IFNAR1 in tumor bearing mice reduces suppressive activity of MDSC and promote antitumor effect. Stabilizing IFNAR1 using inhibitor of p38 combined with the interferon induction therapy elicits a robust anti-tumor effect that is completely dependent on IFNAR1 expression on MDSC. Thus, inhibition of MDSC immune suppressive function can be exploited therapeutically. Citation Format: Emilio Sanseviero, Kevin Alicea-Torres, Yulia Nefedova, Serge Y. Fuchs, Dmitry I. Gabrilovich. Inactivation of IFN signaling drive immunosuppressive MDSC function and can be therapeutically targeted [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2021 Oct 5-6. Philadelphia (PA): AACR; Cancer Immunol Res 2022;10(1 Suppl):Abstract nr P047.