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- Title
Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer.
- Authors
Youn, Je-In; Kumar, Vinit; Collazo, Michelle; Nefedova, Yulia; Condamine, Thomas; Cheng, Pingyan; Villagra, Alejandro; Antonia, Scott; McCaffrey, Judith C; Fishman, Mayer; Sarnaik, Amod; Horna, Pedro; Sotomayor, Eduardo; Gabrilovich, Dmitry I
- 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.
- Subjects
EPIGENETICS; GENE silencing; RETINOBLASTOMA; GENETIC regulation; CANCER cell differentiation; SUPPRESSOR cells; MONOCYTES; IMMUNOREGULATION
- Publication
Nature Immunology, 2013, Vol 14, Issue 3, p211
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.2526