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

JI Youn, V Kumar, M Collazo, Y Nefedova… - Nature …, 2013 - nature.com
JI Youn, V Kumar, M Collazo, Y Nefedova, T Condamine, P Cheng, A Villagra, S Antonia
Nature immunology, 2013nature.com
Two major populations of myeloid-derived suppressor cells (MDSCs), monocytic MDSCs (M-
MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) regulate immune responses in
cancer and other pathologic conditions. Under physiologic conditions, Ly6ChiLy6G−
inflammatory monocytes, which are the normal counterpart of M-MDSCs, differentiate into
macrophages and dendritic cells. PMN-MDSCs are the predominant group of MDSCs that
accumulates in cancer. Here we show that a large proportion of M-MDSCs in tumor-bearing …
Abstract
Two major populations of myeloid-derived suppressor cells (MDSCs), monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs) regulate immune responses in cancer and other pathologic conditions. Under physiologic conditions, Ly6ChiLy6G inflammatory monocytes, which are the normal counterpart of M-MDSCs, differentiate into macrophages and dendritic cells. PMN-MDSCs are the predominant group of MDSCs that accumulates in cancer. Here we show that a large proportion of M-MDSCs in tumor-bearing mice acquired phenotypic, morphological and functional features of PMN-MDSCs. Acquisition of this phenotype, but not the functional attributes of PMN-MDSCs, was mediated by transcriptional silencing of the retinoblastoma gene through epigenetic modifications mediated by histone deacetylase 2 (HDAC-2). These data demonstrate a new regulatory mechanism of myeloid cells in cancer.
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