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

Je In Youn, Vinit Kumar, Michelle Collazo, Yulia Nefedova, Thomas Condamine, Pingyan Cheng, Alejandro Villagra, Scott Antonia, Judith C. McCaffrey, Mayer Fishman, Amod Sarnaik, Pedro Horna, Eduardo Sotomayor, Dmitry I. Gabrilovich

Research output: Contribution to journalArticlepeer-review

205 Scopus citations

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, Ly6C hi Ly6G - 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.

Original languageEnglish (US)
Pages (from-to)211-220
Number of pages10
JournalNature immunology
Volume14
Issue number3
DOIs
StatePublished - Mar 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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