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目的研究舒尼替尼(sunitinib)对肾癌患者外周血单核细胞来源的树突状细胞(DC)表面共刺激分子程序性死亡蛋白配体1(PD-L1)、PD-L2、CD80、CD86、B7-H4及疱疹病毒侵入介体(HVEM)表达的影响。方法体外诱导肾癌患者外周血单核细胞来源的DC,随机分为sunitinib联合LPS组、LPS组及DMSO组。Sunitinib联合LPS组用200 ng/m L sunitinib预处理DC 12 h,再用1μg/m L脂多糖(LPS)刺激24 h;LPS组用1μL/m L DMSO预处理12 h,再用1μg/m L LPS刺激24 h;DMSO组用1μL/m L DMSO作用36 h。倒置显微镜观察各组形态变化;流式细胞术检测DC表面PD-L1、PD-L2、CD80、CD86、B7-H4及HVEM表达变化。结果 Sunitinib联合LPS组和LPS组的DC均呈典型的树枝状突起,DMSO组细胞树突不明显;与LPS组相比,sunitinib联合LPS组表达的CD80、PD-L1及B7-H4显著下降;DMSO组的PD-L1、PD-L2、CD80、CD86、B7-H4及HVEM均呈低水平表达。结论 Sunitinib抑制LPS诱导DC表达CD80、PD-L1、B7-H4。
Objective To investigate the effects of sunitinib on the expression of PD-L1, PD-L2, CD80, CD8 on dendritic cells derived from peripheral blood mononuclear cells in patients with renal cell carcinoma CD86, B7-H4 and herpesvirus invasive mediator (HVEM) expression. Methods DC derived from peripheral blood mononuclear cells of renal cell carcinoma patients were randomly divided into sunitinib group, LPS group and DMSO group. Sunitinib combined with LPS group was pretreated with 200 ng / mL sunitinib for 12 h and then stimulated with 1 μg / mL lipopolysaccharide (LPS) for 24 h. LPS group was pretreated with 1 μL / L LPS stimulation 24 h; DMSO group with 1 μL / m L DMSO for 36 h. The morphological changes of each group were observed by inverted microscope. The expression of PD-L1, PD-L2, CD80, CD86, B7-H4 and HVEM were detected by flow cytometry. Results DCs in Sunitinib combined LPS group and LPS group showed typical dendrites. The dendrites in DMSO group were not obvious. Compared with LPS group, the expression of CD80, PD-L1 and B7-H4 in sunitinib group and LPS group decreased significantly. PD-L1, PD-L2, CD80, CD86, B7-H4 and HVEM in DMSO group all showed low level expression. Conclusions Sunitinib inhibits LPS-induced DC expression of CD80, PD-L1 and B7-H4.