Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer

Two major populations of myeloid-derived suppressor cells (MDSC), monocytic MDSC (M-MDSC) and polymorphonuclear MDSC (PMN-MDSC) regulate immune responses in cancer and other pathologic conditions. Under physiologic conditions, Ly6C(hi)Ly6G(−) inflammatory monocytes, which are the normal counterpart of M-MDSC, differentiate into macrophages and dendritic cells (DCs). PMN-MDSC is the predominant group of MDSC that accumulates in cancer. Here we show that a large proportion of M-MDSC in tumor-bearing mice acquired phenotypic, morphological and functional features of PMN-MDSC. Acquisition of this phenotype, but not the functional attributes of PMN-MDSC, was mediated by transcriptional silencing of the retinoblastoma (Rb) gene through epigenetic modifications mediated by histone deacetylase 2 (HDAC-2). These data demonstrate novel mechanism regulation of myeloid cells in cancer.