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  • Poster presentation
  • Open Access

Loss of Rb1 by epigenetic modification regulates expansion of MDSC in cancer

  • 1,
  • 1,
  • 1 and
  • 2
Journal for ImmunoTherapy of Cancer20142 (Suppl 3) :P241

https://doi.org/10.1186/2051-1426-2-S3-P241

  • Published:

Keywords

  • Retinoblastoma
  • Histone Acetylation
  • HDAC Inhibitor
  • Epigenetic Modification
  • Suppressor Cell

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of cells with potent immune suppressive activity in cancer and many other pathologic conditions. MDSCs consist of two major subsets: monocytic MDSCs (M-MDSCs) and polymorphonuclear MDSCs (PMN-MDSCs). Each subset of MDSCs is thought to be developed through the separate differentiation pathways. Here, we demonstrated that in a tumor environment a large proportion of M-MDSCs acquired phenotypic, morphological and functional features of PMN-MDSCs while the normal counterpart of M-MDSCs-Ly6ChiLy6G- inflammatory monocytes (Mon) from tumor-free mice differentiate to macrophages (MΦ) and dendritic cells (DCs). This process was mediated by loss of the retinoblastoma (Rb1) protein in MDSCs. Inhibition of Rb1 expression in PMN-MDSCs correlated with the level of histone acetylation of Rb1 promoter. Treatment of PMN-MDSCs with inhibitors of histone deacetylases (HDAC) resulted in the increase in Rb1 expression. In addition, inhibition of HDAC abrogated differentiation of M-MDSCs to PMN-MDSCs, and restored M-MDSCs differentiation towards DCs and MΦ. These results suggest that down-regulation of Rb1 by epigenetic modification plays a major role in expansion of MDSCs in cancer by regulating PMN-MDSCs differentiation from M-MDSCs. Therefore, inhibition of MDSCs accumulation by treatment of HDAC inhibitors may be considered as a potential therapeutic tool in cancer immunotherapy.

Authors’ Affiliations

(1)
Wide River Institute of Immunology, Seoul National University, Republic of Korea
(2)
The Wistar Institute, Philadelphia, PA, USA

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