FcγRIIb deficiency inhibits tumor development by attenuating the immunosuppressive phenotype of MDSCs.

Regulation of myeloid-derived suppressor cell (MDSC) programming is critical for controlling tumor growth and anti-tumor immune responses. The role of FcγRIIb in MDSC programming was examined. FcγRIIb deficiency was found to promote MDSC differentiation and increase splenic MDSC accumulation in tumor-bearing mice. This deficiency also attenuated the immunosuppressive phenotype of both polymorphonuclear (PMN)-MDSCs and monocytic (M)-MDSCs. Tumor growth in FcγRIIb mice was significantly lower than in wild-type (WT) mice. Adoptive transfer of FcγRIIb MDSC subsets following B16F10/3LL injection significantly delayed tumor growth compared with transfer of WT MDSC subsets. Activation of the NF-κB pathway was observed in FcγRIIb MDSCs, which was associated with the diminished immunosuppressive phenotype. In human MDSCs, FcγRIIb expression was associated with the progression of lung cancer. These findings demonstrate that FcγRIIb is crucial for the immunosuppressive phenotype of MDSCs and may serve as a potential therapeutic target for anti-tumor therapy.