树突状细胞联合细胞因子介导杀伤细胞免疫治疗肾癌临床研究

Immunotherapy using dendritic cells and cytokine-induced killer for kidney cancer

目的:探讨以树突状细胞(dendritic cells,DC)联合细胞因子介导杀伤细胞(cytokine induced killer,CIK)为基础的免疫途径治疗恶性实体肿瘤的临床疗效。方法:将60例临床确诊的肾透明细胞癌患者随机分为两组:治疗组给予手术联合细胞免疫治疗,对照组给予手术及细胞因子治疗。采集肿瘤患者的外周血单核细胞,体外诱导培养成熟DC及CIK细胞,最后再回输给患者。观察疗效和治疗前后细胞免疫指标变化(CD3^+、CD4^+、CD8^+、CD4^+/CD8^+、NK细胞)、外周血象、肝肾功能变化(白细胞、转氨酶、尿素氮、肌酐)及不良反应。结果:治疗组有效率43.33%,对照组有效率26.67%,治疗组与对照组相比,差异有统计学意义(P<0.05)。治疗组CD3^+、CD4^+、CD4^+/CD8^+免疫学指标治疗前后比较,差异有统计学意义(P值分别为0.010,0.026,0.021),治疗组细胞免疫学指标(CD3^+、CD4^+、CD4^+/CD8^+)在治疗前后变化与对照组相比,结果差异有统计学意义(P值分别为0.001,0.023,0.012)。两组患者外周血象及肝肾功能检测无异常,免疫治疗过程中未出现明显的毒副作用。结论:以DC、CIK细胞为基础的细胞免疫治疗可以明显改善肾癌术后患者临床疗效,提高外周血淋巴细胞亚群及NK细胞水平,临床应用无明显不良反应,是肾癌术后重要的辅助治疗手段。

Objective：To investigate the clinical efficacy of immunotherapy using dendritic cells（DC） and cytokine-induced killer （CIK）in treatment of patients with kidney cancer. Methods： Sixty patients with kidney cancer were divided into 2 groups randomly ： the control group and immunotherapy group. Peripheral blood mononuclear cells （PBMC） were seperated from the patients who received immunotherapy first, then DC and CIK were induced and cultured with GM-CSF and IL-4 in vitro. The immunotherapy group received DC four times and CIK twice at an interval of 14 days after routine treatment. The control group received only chemotherapy. T lymphocyte subtypes and NK cells in peripheral blood, the white ceils and the values of liver and kidney biochemistry of two group of patients were analyzed and clinical efficacy were observed, so were side effects. Results： Clinical efficacy showed significant statistical difference between the two groups （P 〈 0.05）. No side effects were observed. The levels of CD3 ^＋ , CD4 ^＋ , CD4^＋/CD8^＋ and NK cell in the immunotherapy group increased after treatment, which showed significant statistical difference compared with those before treatment（P value was 0. 010,0.026,0. 021, 0. 016, respectively）. Changes in cell immune indexes （ CD3 ^＋ , CD4 ^＋ , CD4 ^＋/CD8 ^＋ ） in immunotherapy group and control group showed significant statistical difference （P value was 0. 001,0. 023,0. 012, respectively）. Conclusion：Immunotherapy using dendritic cells and cytokine-induced killer combined with routine treatment can improve T lymphocyte subtypes and NK cell ratio in peripheral blood of the patients with kidney cancer,and may play an important role in the treatment of kidney cancer. It can enhance clinical efficacy in patients with kidney cancer and can improve prog