Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice
Long noncoding RNA Pvt1 regulates the immunosuppression activity of granulocytic myeloid-derived suppressor cells in tumor-bearing mice
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长非编码RNA Pvt1调节荷瘤小鼠粒细胞骨髓源性抑制细胞的免疫抑制活性
DOI：
10.1186/s12943-019-0978-2
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发表时间：
2019-03-30
期刊：
影响因子：
37.3
通讯作者：
Wang, Shengjun
中科院分区：
文献类型：
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作者：
Zheng, Yu;Tian, Xinyu;Wang, Shengjun
背景髓源性抑制细胞(MDSCs)通过显著阻断T细胞诱导的抗肿瘤反应，参与肿瘤免疫抑制，从而影响肿瘤免疫治疗的效果。改变MDSCs分化和功能的治疗可以部分恢复抗肿瘤免疫反应。长非编码RNA浆细胞瘤变异体易位1(LncRNA PVT1)是一种在多种癌症类型中潜在的癌基因。然而，目前尚不清楚lncRNA PVT1是否参与MDSCs的调控。方法采用微球和流式细胞术分离MDSCs或粒细胞MDSCs。骨髓来源的G-MDSCs用IL-6和GM-CSF诱导。用qRT-PCR方法检测pCNRNAPVT1的表达。用特异性siRNA抑制G-MDSCs中lncRNA PVT1的表达。此外，在体内，lncRNA PVT1基因敲除降低了G-MDSCs延缓荷瘤小鼠肿瘤进展的能力。结论在缺氧条件下，lncRNAPVT1在调节G-MDSCs免疫抑制活性中起重要作用，lncRNAPVT1可能成为潜在的抗肿瘤免疫治疗靶点。
BackgroundMyeloid-derived suppressor cells (MDSCs) participate in tumor-elicited immunosuppression by dramatically blocking T-cell-induced antitumor responses, thereby influencing the effectiveness of cancer immunotherapies. Treatments that alter the differentiation and function of MDSCs can partially restore antitumor immune responses. The long noncoding RNA plasmacytoma variant translocation 1 (lncRNA Pvt1) is a potential oncogene in a variety of cancer types. However, whether lncRNA Pvt1 is involved in the regulation of MDSCs has not been thoroughly elucidated to date.MethodsMDSCs or granulocytic MDSCs (G-MDSCs) were isolated by microbeads and flow cytometry. Bone marrow derived G-MDSCs were induced by IL-6 and GM-CSF. The expression of lncRNA Pvt1 was measured by qRT-PCR. Specific siRNA was used to knockdown the expression of lncRNA Pvt1 in G-MDSCs.ResultsIn this study, we found that knockdown of lncRNA Pvt1 significantly inhibited the immunosuppressive function of G-MDSCs in vitro. Additionally, lncRNA Pvt1 knockdown reduced the ability of G-MDSCs to delay tumor progression in tumor-bearing mice in vivo. Notably, lncRNA Pvt1 was upregulated by HIF-1α under hypoxia in G-MDSCs.ConclusionsTaken together, our results demonstrate a critical role for lncRNA Pvt1 in regulating the immunosuppression activity of G-MDSCs, and lncRNA Pvt1 might thus be a potential antitumor immunotherapy target.