Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer.
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.
Departments of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA.
Je-In
JI
Youn
Vinit
V
Kumar
Michelle
M
Collazo
Yulia
Y
Nefedova
Thomas
T
Condamine
Pingyan
P
Cheng
Alejandro
A
Villagra
Scott
S
Antonia
Judith C
JC
McCaffrey
Mayer
M
Fishman
Amod
A
Sarnaik
Pedro
P
Horna
Eduardo
E
Sotomayor
Dmitry I
DI
Gabrilovich
D000818:Animals; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000276:immunology; D044127:Epigenesis, Genetic; D020868:Gene Silencing; D016161:Genes, Retinoblastoma; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D022423:Myeloid Cells / Q000378:metabolism / Q000473:pathology*; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D016160:Retinoblastoma Protein / Q000235:genetics
D016160:Retinoblastoma Protein