泊马度胺对慢性粒细胞白血病患者单核细胞起源树突状细胞成熟的影响

Effect of pomalidomide on the maturation of monocyte-derived dendritic cells in patients with chronic myelogenous leukemia

目的:探索泊马度胺对慢性粒细胞白血病(chronic myelogenous leukemia,CML)患者单核细胞起源树突状细胞(monocyte derived dendritic cells,moDCs)成熟/活性的影响。方法:分别采集长期服用伊马替尼(n=10)、尼洛替尼(n=10)和达沙替尼(n=9)治疗的CML患者外周血,体外诱导培养其中单核细胞形成树突状细胞(moDCs),该过程中给予10μmol·L^(-1)泊马度胺或等量药物溶媒处理。流式检测moDCs表面成熟/活性相关标志物CD40、CD83和HLA-DR的表达,流式液相多重蛋白定量技术检测细胞培养上清液中DC活性相关细胞因子IL-6和MIP-1α的分泌。结果:与对照组相比,泊马度胺分别显著提高了伊马替尼、尼洛替尼和达沙替尼治疗的CML患者moDCs上CD40、CD83和HLA-DR的表达比例(均为P<0.05)。分析整体29例CML患者moDCs,结果显示泊马度胺显著提高了DC活性相关细胞因子IL-6和MIP-1α的分泌浓度(均为P<0.05)。结论:10μmol·L^(-1)泊马度胺在体外可有效促进长期服用伊马替尼、尼洛替尼或达沙替尼治疗CML患者moDCs的成熟/活性,其有望作为DC佐剂应用于以DC为基础的免疫治疗策略中,如DC抗肿瘤疫苗及DC细胞治疗。

OBJECTIVE To explore the effect of pomalidomide on the maturation/activity of monocyte-derived dendritic cells(moDCs)in chronic myelogenous leukemia(CML)patients.METHODS Peripheral blood samples were collected from CML patients treated with long-term use of imatinib(n=10),nilotinib(n=10)and dasatinib(n=9),respectively.Monocyte-derived dendritic cells were cultured in vitro and treated with 10μmol·L-1 pomalidomide or the same amount of drug solvent.The expression of maturation/activity related markers CD40,CD83 and HLA-DR on the surface of moDCs was detected by flow cytometry.The secretion of DC activity-related cytokines IL-6 and MIP-1αin the cell culture supernatant was detected by cytometric beads array.RESULTS Compared with the control group,the experiment group(pomalidomide group)significantly enhanced the expression ratio of the surface marker CD40,CD83 and HLA-DR on the CML patients’moDCs treated with imatinib,nilotinib and dasatinib,respectively(all P<0.05).When analyzing the moDCs from all the 29 CML patients together,pomalidomide was also observed to significantly enhance the secretion concentration of IL-6 and MIP-1αcompared with the control group(all P<0.05).CONCLUSION 10μmol·L-1 pomalidomide can effectively promote the maturation/activity of CML patients’moDCs treated with long-term use of imatinib,nilotinib and dasatinib,respectively in vitro,which is expected to be used as a promising DC adjuvant in DC-based immunotherapy strategies,such as DC anti-tumor vaccine and DC cell therapy.