来那度胺增强细胞因子诱导的杀伤细胞杀伤效应的研究

Lenalidomide enhances anti-tumor effects of CIK cells against lymphoma

目的探讨来那度胺调节细胞因子诱导的杀伤（CIK）细胞对淋巴瘤细胞的杀伤效应。方法取健康志愿者外周血单个核细胞，经过干扰素-γ（INF-γ）、白细胞介素-2（IL-2）、抗CD3单抗诱导CIK细胞增殖，并对培养不同时间CIK细胞用不同浓度来那度胺进行处理。流式细胞术检测CD；CD；6细胞比例；酶联免疫吸附（ELISA）法检测粒．巨噬细胞集落刺激因子（GM-CSF）、INF-γ及肿瘤坏死因子α（TNF—α）的分泌水平；用CellCountingKit-8（CCK-8）试剂盒检测来那度胺作用后的CIK细胞及未处理的CIK细胞对3种淋巴瘤细胞株的体外杀伤效应。结果CIK细胞在多种细胞因子诱导下，CD3 CD56细胞比例明显增加，0．2～5．0μmol／L的来那度胺对其扩增分化没有影响（P〉0．05）。来那度胺作用下CIK细胞分泌GM—CSF、INFμ、TNF-α水平有显著提高（P〈0．05）。在1．0μmol／L来那度胺作用下CIK细胞对淋巴瘤细胞的杀伤效力明显高于未经来那度胺处理的CIK细胞[（42．53±2．19）％比（15．5±3．82）％；（44．78±4．86）％比（29．94±6．33）％；（54．71±5．31）％比（37．43±9．75）％1。结论在来那度胺作用下，CIK细胞分泌功能和对3种淋巴瘤细胞的杀伤效应均有显著增强。

ObJective To investigate lenalidomide modulates anti-tumor effects of cytokine induced killer（CIK） cells against lymphoma cells in vitro. Methods CIK cells were generated in vitro by stimulation of health donors＇ peripheral blood mononuclear cells subsets with interferon-gamma（INF-γ）, IL-2 and anti-CD3 monoelonal antibody. On the different culture time CIK cells were treated with different concentrations of lenalidomide. CD;CD;6 cell ratio was detected by flow cytometry and ELISA method was used for the detection of GM-CSF, INF-γ and TNF-α level of secretion. Inhibitory effects of CIK cells and CIK cells treated by lenalidomide on the three types of lymphoma cell lines were detected by cell counting kit-8（CCK-8）. Results Amount of CD3CD56 cells were increased without inhibition by lenalidomide at 0.2-5.0μmol/L （P〉0.05）. Lenalidomide led to significantly higher levels of GM-CSF, INF-γ and TNF-α secreted by CIK cells （P〈0.05） . On different culture time C1K cells treated by 1.0 μmol/L lenalidomide had higher killing effects on Z-138 [（42.53±2.19） % vs（15.5±3.82） %], Jurkat[（44.78±4.86） % vs（29.94±6.33） %], RPMI 8226 cells [（54.71± 5.31） % vs（37.43±9.75） %]than that without lenalidomide treating（P〈0.05）.Conelusion Lenalidomide can enhance killing effect of CIK cells on lymphoma cell lines in vitro.