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

doi:10.1038/ni.2526

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

Laboratory Medicine and Pathology

Research output: Contribution to journal › Article › peer-review

214 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 language	English (US)
Pages (from-to)	211-220
Number of pages	10
Journal	Nature immunology
Volume	14
Issue number	3
DOIs	https://doi.org/10.1038/ni.2526
State	Published - Mar 2013

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Youn, J. I., Kumar, V., Collazo, M., Nefedova, Y., Condamine, T., Cheng, P., Villagra, A., Antonia, S., McCaffrey, J. C., Fishman, M., Sarnaik, A., Horna, P., Sotomayor, E., & Gabrilovich, D. I. (2013). Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer. Nature immunology, 14(3), 211-220. https://doi.org/10.1038/ni.2526

Youn, JI, Kumar, V, Collazo, M, Nefedova, Y, Condamine, T, Cheng, P, Villagra, A, Antonia, S, McCaffrey, JC, Fishman, M, Sarnaik, A, Horna, P, Sotomayor, E & Gabrilovich, DI 2013, 'Epigenetic silencing of retinoblastoma gene regulates pathologic differentiation of myeloid cells in cancer', Nature immunology, vol. 14, no. 3, pp. 211-220. https://doi.org/10.1038/ni.2526

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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.",

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

note = "Funding Information: We thank A. Beg (H. Lee Moffitt Cancer Center) for providing us with Kras/mCC10 mice and D.J. McCance (Queen{\textquoteright}s University Belfast, UK) for providing us with Ad-Rb1 vectors. This work was supported by US National Institutes of Health grant CA84488.",

year = "2013",

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doi = "10.1038/ni.2526",

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AU - Cheng, Pingyan

AU - Villagra, Alejandro

AU - Antonia, Scott

AU - McCaffrey, Judith C.

AU - Fishman, Mayer

AU - Sarnaik, Amod

AU - Horna, Pedro

AU - Sotomayor, Eduardo

AU - Gabrilovich, Dmitry I.

N1 - Funding Information: We thank A. Beg (H. Lee Moffitt Cancer Center) for providing us with Kras/mCC10 mice and D.J. McCance (Queen’s University Belfast, UK) for providing us with Ad-Rb1 vectors. This work was supported by US National Institutes of Health grant CA84488.

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

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