西达本胺对急性T淋巴细胞白血病CD8^(+)T细胞的调控作用研究

Study on the Regulation of Chidamide on CD8^(+)T Cells in T-cell Acute Lymphoblastic Leukemia

目的:探讨西达本胺对急性T淋巴细胞白血病CD8+T细胞的调控作用。方法:通过荧光定量PCR检测西达本胺处理的Jurkat细胞、淋巴细胞、与西达本胺处理的Jurkat细胞共培养的淋巴细胞的CXCL9、CXCL3 m RNA表达水平。通过流式细胞术检测西达本胺处理的淋巴细胞、与西达本胺处理的Jurkat细胞共培养的淋巴细胞中CD8+T细胞的比例。结果:西达本胺上调Jurkat细胞系CXCL9的m RNA表达,上调水平呈剂量依赖(r=0.950),西达本胺5μmol/L组的CXCL9 m RNA表达是无处理组的164倍。西达本胺上调淋巴细胞CXCL9的m RNA表达,上调水平明显低于同浓度西达本胺处理的Jurkat细胞系。与西达本胺处理的Jurkat细胞共培养,可以上调淋巴细胞中CD8+T细胞的比例。结论:急性T淋巴细胞白血病中,西达本胺可能通过上调肿瘤细胞CXCL9的表达,增加肿瘤微环境中CXCL9的浓度,导致CD8+T细胞数量的增加。

Objective:To explore the regulatory effect of chidamide on CD8+T cells in T-cell acute lymphoblastic leukemia.Methods:The expression levels of CXCL9 and CXCL3 m RNA in Jurkat cells,lymphocytes treated with chidamide and lymphocytes co-cultured with chidamide-treated Jurkat cells were detected by fluorescence quantitative PCR.The proportion of CD8+T cells in lymphocytes treated with chidamide and lymphocytes co-cultured with chidamide-treated Jurkat cells was determined by flow cytometry.Results:Chidamide upregulated CXCL9 m RNA expression in Jurkat cell line in a dose-dependent manner (r=0.950).The m RNA expression of CXCL9 in chidamide5μmol/L group was 164 times higher than that in control group.Chidamide upregulated CXCL9 m RNA expression in lymphocytes,but the up-regulated level was significantly lower than that in Jurkat cell line treated with the same concentration of chidamide.Co-culture with chidamide treated Jurkat cells upregulated the proportion of CD8+T cells in lymphocytes.Conclusion:In T-cell acute lymphoblastic leukemia,chidamide may increase the concentration of CXCL9in the tumor microenvironment by up-regulating the expression of CXCL9 in tumor cells,leading to an increase in the number of CD8+T cells.