Fig. 4.

Epigenetic regulation in myeloid-derived suppressor cells. DNMT3A is upregulated in MDSCs and methylates genes, including S1PR4, RUNX1, IL1RN, and CCR2, to create unique DNA methylation patterns during MDSC differentiation. HDAC11 is a negative regulator of MDSC expansion/function. HMT SET1B controls MDSC function through upregulation of iNOS. HDAC activation facilitates immunosuppression and myeloid cell recruitment of immature MDSCs through the activation of ARG1, CCR2, and ITGAL. HDAC2 regulates MDSC differentiation and immunosuppressive function by modulating Rb1 expression. CBP/EP300-BRD, with its intrinsic histone acetyltransferase activity, reprograms tumor-associated MDSCs from expressing a suppressive to expressing an inflammatory phenotype through downregulation of STAT pathway-related genes such as Ly6C2, Ccr2, Mmp9, and NOS2 and the inhibition of Arg1 and iNOS