自体树突细胞联合细胞因子诱导的杀伤细胞治疗晚期非小细胞肺癌的临床研究  

Autologous dendritic cells combined with cytokine-induced killer cells in the treatment of advanced non-small-cell lung carcinoma

作　　者：丁国梁[1] 张金超[1] 王丹红[1] 陈虎[1] 

机构地区：[1]军事医学科学院附属医院造血干细胞移植科,北京100071

出　　处：《解放军医学杂志》2017年第9期799-804,共6页Medical Journal of Chinese People's Liberation Army

基　　金：国家科技重大专项"十二五"计划基金资助项目(2009ZX09503)~~

摘　　要：目的评价自体树突细胞(DC)联合细胞因子诱导的杀伤细胞(CIK)治疗晚期非小细胞肺癌的临床疗效和安全性。方法采集39例晚期非小细胞肺癌患者的外周血单个核细胞(PBMC),经实验室体外培养诱导产生DC和CIK细胞,经流式细胞术进行表型鉴定后回输给患者。于第7、9、11、13天皮下注射DC,第11、13天静脉回输CIK。比较39例患者治疗前后的临床疗效、免疫功能并评价安全性。结果 39例患者中,完全缓解(CR)2例,部分缓解(PR)10例,稳定(SD)15例,进展(PD)12例;39例患者经DC-CIK治疗后的客观反应率为30.7%,疾病控制率为69.2%。接受≥2个疗程免疫治疗的患者生存率明显高于接受1个疗程的患者。与治疗前比较,治疗后患者外周血CD3^+CD4^+CD8–、CD3^+CD4–CD8^+、CD3^+CD19–、CD3–CD19^+、CD3–CD16^+CD56^+、CD3^+CD16^+CD56^+、CD3^+HLA-DR–、CD3^+HLA-DR^+、CD3^+CD28^+CD8^+细胞亚群的比例无明显变化(P>0.05),Th1细胞、Th2细胞比例明显升高,CD3^+CD4^+CD25^+T细胞(即调节性T细胞,Treg细胞)比例明显降低,差异均有统计学意义(P<0.05)。治疗过程中,39例患者均未出现明显不良反应。结论 DC-CIK细胞免疫治疗为晚期非小细胞肺癌提供了一种新的安全有效的治疗选择,可有效改善患者的免疫抑制状态,提高抗肿瘤免疫反应,降低肿瘤复发和转移的可能性。Objective To evaluate the clinical efficacy and safety of dendritic cell （DC） combined with cytokine induced killer cell （CIK） in treatment of advanced non-small-cell lung carcinoma （NSCLC）. Methods Peripheral blood mononuclear cells （PBMCs） were collected from 39 patients with advanced NSCLC, who were admitted to Affiliated Hospital of Academy of Military Medical Sciences, and cultured in vitro to produce DCs and CIK cells which, after phenotypic characterization by flow cytometry, were then returned to the patients. DCs were given subcutaneously on day 7, 9, 11 and 13 and CIK cells were given intravenously on day 11 and 13. The clinical efficacy and safety were analyzed before and after DCs-CIK cells treatment. Results Following up displayed that, in 39 patients with advanced NSCLC and eligible for evaluation, the objective response rate （ORR） was 30.8% including 2 cases of completed response （CR） and 10 cases of partial response （PR）, the disease control rate （DCR） was 69.2%. No significant difference existed pre- and post-treatment on the proportion of T cell subsets including CD3＋CD4＋CD8-, CD3＋CD4- CD8＋, CD3＋CD19-, CD3-CD 19＋, CD3-CD16＋CDS6＋, CD3＋CD16＋D56＋, CD3＋HLA-DR-, CD3＋HLA-DR＋ and CD3＋CD28＋CD8＋ （P〉0.05）, while obvious changes were found in Thl, Th2 and CD3＋CD4＋CD25＋ T cells （Treg cells） （P〈0.05）. No serious adverse events were observed. Conclusion Combined DCs-CIK cells immunotherapy provides a safe and effective treatment for patients with advanced NSCLC, improves the quality of life and relieves the probability of metastasis and recurrence.

关 键 词：树突状细胞 细胞因子诱导杀伤细胞 癌 非小细胞肺 

分 类 号：R734.2[医药卫生—肿瘤]