DC－CIK联合化疗对多发性骨髓瘤患者细胞免疫功能的影响

摘要

目的：研究树突状细胞（ DC）和细胞因子诱导的杀伤细胞（ CIK）为效应细胞的过继免疫联合化疗治疗多发性骨髓瘤（ MM）的临床疗效及对患者外周血T细胞亚群、CD4＋CD25＋调节性T（ Treg）细胞的影响，从而探讨以上治疗对MM患者的细胞免疫调节功能。方法：将50例MM患者随机分为两组：化疗组24例，给予合适的化疗方案；联合组26例，除接受适合的化疗外，还给予DC／CIK免疫治疗，比较两组患者的临床疗效及外周血T细胞亚群、CD4＋CD25＋调节性T（ Treg）细胞比例，并比较两组患者细胞免疫指标（ Th1／Th2比值、AgNORs比值、TGF－β）的差异。结果：3周期治疗后，联合组患者的生活质量和临床疗效[PS评分为2．10±0．49；瘤细胞百分比为（28．55±7．11）％；β2微球蛋白表达水平为（10．21±3．03）mg／L；血清M蛋白水平为（27．11±6．87）g／L；24h尿液轻链为（9．11±3．66）mg；肌酐水平为（159．33±29．68）μmol／L]均优于化疗组患者[2．59±0．52；（37．34±12．89）％；（17．22±4．21）mg／L；（35．26±12．32）g／L ；（14．87±4．06）mg；（254．19±37．46）μmol／L]（P值均＜0．05）。联合组CD3＋CD8＋比例[（24．68±7．38）％]、CD4＋CD25＋[（1．22±0．26）％]、CD4＋CD25＋／CD4＋[（3．58±1．69）％]、TGF－β含量[（1．32±0．39）ng／mL]均明显低于化疗组[（27．56±6．59）％、（1．45±0．40）％、（4．67±2．77）％、（1．49±0．59） ng／mL]（P＜0．05）；CD3＋CD4＋／CD3＋CD8＋比值[（1．46±0．33）％]、Th1／Th2比值（1．49±0．29）、AgNOR比值[（5．06±0．69）IS％]均明显高于化疗组[（1．38±0．28）％、（1．32±0．31）、（4．37±0．67）IS％]（P＜0．05），提示联合治疗组对MM具有更有效的免疫调节功能。结论：DC／CIK免疫治疗联合化疗治疗MM有良好的临床疗效和应用价值，可能通过免疫调节使MM患者Th2向Th1逆转，从而增强机体抗肿瘤效应。%Objective:To valuate the treatment value and analyse the effect on the cellular immune functions by studying the differences of T-lymphocyte subsets and CD4+CD25+Treg cells in peripheral blood after adoptive immunotherapy ( dendritic cells and cytokine-induced killer cells,DC-CIK) combined with chemotherapy on MM.Methods:50 patients with MM were randomly divided into two groups.24 patients in chemotherapy group were treated by chemotherapy only,26 patients in joint group were treated by adoptive immunotherapy( DC-CIK) combined with chemotherapy,and the clinical outcomes and the levels of T-lymphocyte subsets and CD4+CD25+Treg cells in peripheral blood between two groups were compared.Moreover,the differences of cellular immune indicators (Th1/Th2,the ratio of AgNOR,and TGF-β)between two groups were also compared.Results: After treatment,quality of life,clinical index and survival in joint group were better than in chemotherapy group( P<0.05);the proportion of CD3+CD8+,the ratios of CD4+CD25+,CD4+CD25+/CD4+and the level of TGF-βof joint group wes clearly lower than chemotherapy group(P<0.05),and the ratios of CD3+CD4+/CD3+CD8+, Th1/Th2 and AgNOR of joint group wes clearly higher than chemotherapy group .Conclusion: DC-CIK combined with chemotherapy could be an effective and promising treatment to patients with MM,and it maybe strengthen the anti-tumor action of bodies by regulating the balance between Th1 and Th2 reaction.