Tumor-induced myeloid-derived suppressor cell function is independent of IFN-γ and IL-4Rα

Myeloid-derived suppressor cells (MDSCs) are present in most cancer patients and experimental animals where they exert a profound immune suppression and are a significant obstacle to immunotherapy. IFN-? and IL-4 receptor alpha (IL-4Ra) have been implicated as essential molecules for MDSC development and immunosuppressive function. If IFN-? and IL-4Ra are critical regulators of MDSCs, then they are potential targets for preventing MDSC accumulation or inhibiting MDSC function. Because data supporting a role for IFN-? and IL-4Ra are not definitive, we have examined MDSCs induced in IFN-?-deficient, IFN-?R-deficient, and IL-4Ra-deficient mice carrying three C57BL/6-derived (B16 melanoma, MC38 colon carcinoma, and 3LL lung adenocarcinoma), and three BALB/c-derived (4T1 and TS/A mammary carcinomas, and CT26 colon carcinoma) tumors. We report that although MDSCs express functional IFN-?R and IL-4Ra, and have the potential to signal through the STAT1 and STAT6 pathways, respectively, neither IFN-? nor IL-4Ra impacts the phenotype, accumulation, or T-cell suppressive potency of MDSCs, although IFN-? and IL-4Ra modestly alter MDSC-macrophage IL-10 crosstalk. Therefore, neither IFN-? nor IL-4Ra is a key regulator of MDSCs and targeting these molecules is unlikely to significantly alter MDSC accumulation or function.