| 谢宏俊,阙滔滔,魏 毅,等.肾细胞癌PBRM1表达缺失抑制CD8+ T细胞浸润[J].肿瘤学杂志,2022,28(7):579-585. |
| 肾细胞癌PBRM1表达缺失抑制CD8+ T细胞浸润 |
| PBRM1 Deletion Inhibits CD8+ T Cells Infiltration in Tumor Microenvironment of Renal Cell Carcinoma |
| 投稿时间：2022-02-21 |
| DOI：10.11735/j.issn.1671-170X.2022.07.B009 |
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| 中文关键词: 肾细胞癌 PBRM1 外泌体 CD8+T细胞 EZH2 |
| 英文关键词:renal cell carcinoma PBRM1 exosome CD8+T cell EZH2 |
| 基金项目:国家自然科学基金(82072829)，陕西省自然科学基础研究计划-面上项目(2021JM-265) |
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| 中文摘要: |
| 摘 要：［目的］ 探讨PBRM1调控CD8+T在肾透明细胞癌组织中细胞浸润的分子机制。［方法］ 以肾透明细胞癌患者肿瘤临床标本为研究对象，探讨CD8+T细胞在人肾癌中的浸润及其与临床病理特征的关系，以免疫印迹、荧光免疫、ELISA等分子生物学方法明确PBRM1调控CD8+T细胞浸润的分子机制。免疫荧光检测CD63、EZH2及PHK26在细胞中的分布。免疫印迹检测IFN-γ，IL-6和TNF-α不同因子处理对肾癌细胞EZH2的诱导表达。实验结果经GraphPad Prism软件， t检验对两组间差异进行统计学分析。［结果］ 肾透明细胞癌组织免疫组化结果显示，在肿瘤组织中CD8+T细胞浸润数量显著性下降(P<0.001)，CD8+T细胞浸润与患者总生存期呈正相关(P<0.001)。患者肿瘤组织PBRM1着色和CD8+T细胞浸润数量结果显示：PBRM1表达与CD8+T细胞浸润数量呈正相关(P<0.001)。IFN-γ，IL-6和TNF-α细胞因子促进EZH2在细胞表达升高，同时被外泌体包载被运输到受体细胞，外泌体EZH2进入受体细胞抑制CXCL9和CXCL10细胞因子分泌。［结论］ PBRM1缺失激活exo-EZH2/CXCL9(10)信号轴抑制CD8+T细胞肿瘤组织浸润。 |
| 英文摘要: |
| Abstract：［Objective］ To explore the molecular mechanism of PBRM1 in regulating CD8+T cell infiltration in clear cell renal cell carcinoma tissue. ［Methods］ The expression of PBRM1 in renal clear cell carcinoma were detected by tissue microarray and its relation with CD8+T cell infiltration in tumor microenvironment was analyzed. Western blot was also applied to detect EZH2 expression after IFN-γ， IL-6 and TNF-α treatment in renal cell carcinoma cells. Immunofluorescence was used to detect the distribution of CD63， EZH2 and PHK26 in cells. The effect of EZH2 on CXCL9/10 secretion was detected by ELISA assay. The GraphPad Prism software was used for statistical analysis. ［Results］ Tissue microarray results showed that the infiltration density of CD8+T cells in tumor tissues was lower than that in adjacent tissues(P<0.001). High CD8+T cell infiltration was positively correlated with the overall survival of patients(P<0.001)， and low PBRM1 protein expression was associated with decreased infiltration of CD8+T cells(P<0.001). IFN-γ， IL-6 and TNF-α promoted the expression of EZH2 protein， which was packaged in exosomes and entered into recipient cells to inhibit CXCL9 and CXCL10 secretion. ［Conclusion］ PBRM1 deletion activates the exo-EZH2/CXCL9(10) signal axis and inhibits CD8+T cell tumor tissue infiltration in renal cell carcinoma. |
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