Myeloid-derived suppressor cells (MDSCs) are derived from bone marrow progenitor cells commonly, which is a heterogeneous cell group composed of immature granulocytes, dendritic cells, macrophages and early undifferentiated bone marrow precursor cells. Its differentiation and immunosuppressive function are regulated by complex network signals, but the specific regulation mechanisms are not yet fully understood. In this study, we found that in mouse of Lewis lung cancer xenograft, long non-coding RNA Snhg6 (lncRNA Snhg6) was highly expressed in tumor-derived MDSCs compared with spleen-derived MDSCs. LncRNA Snhg6 facilitated the differentiation of CD11b+ Ly6G− Ly6Chigh monocytic MDSCs (Mo-MDSCs) rather than CD11b+ Ly6G+ Ly6Clow polymorphonuclear MDSCs (PMN-MDSCs), but did not affect the immunosuppressive function of MDSCs. Notably, lncRNA Snhg6 could inhibit the expression of EZH2 by ubiquitination pathway at protein level rather than mRNA level during the differentiation of mouse bone marrow cells into MDSCs in vitro. EZH2 may be an important factor in the regulation of lncRNA Snhg6 to promote the differentiation of Mo-MDSCs. So what we found may provide new ideas and targets for anti-tumor immunotherapy targeting MDSCs.

中文翻译：

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LncRNA Snhg6通过调节EZH2的泛素化来调节MDSCs的分化

髓源性抑制细胞（MDSCs）通常来源于骨髓祖细胞，是由未成熟粒细胞、树突状细胞、巨噬细胞和早期未分化的骨髓前体细胞组成的异质细胞群。其分化和免疫抑制功能受复杂的网络信号调控，但具体调控机制尚不完全清楚。在本研究中，我们发现在 Lewis 肺癌异种移植小鼠中，与脾源性 MDSCs 相比，长链非编码 RNA Snhg6 (lncRNA Snhg6) 在肿瘤源性 MDSCs 中高表达。LncRNA Snhg6 促进了 CD11b+ Ly6G− Ly6Chigh 单核细胞 MDSCs (Mo-MDSCs) 而不是 CD11b+ Ly6G+ Ly6Clow 多形核 MDSCs (PMN-MDSCs) 的分化，但不影响 MDSCs 的免疫抑制功能。尤其，lncRNA Snhg6在小鼠骨髓细胞体外向MDSCs分化过程中，可通过泛素化途径在蛋白水平而非mRNA水平上抑制EZH2的表达。EZH2可能是调控lncRNA Snhg6促进Mo-MDSCs分化的重要因子。因此，我们的发现可能为针对 MDSC 的抗肿瘤免疫治疗提供新的思路和靶点。