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Volume 2 Supplement 3

Abstracts of the 29th Annual Scientific Meeting of the Society for Immunotherapy of Cancer (SITC)

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

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.

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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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Youn, JI., Lee, K., Lee, HC. et al. Loss of Rb1 by epigenetic modification regulates expansion of MDSC in cancer. j. immunotherapy cancer 2 (Suppl 3), P241 (2014).

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