DC-CIK细胞联合治疗158例恶性肿瘤的免疫疗效观察

The immune efficacy of DCs combined with CIK cells on malignant tumors

目的探讨树突状细胞(DCs)与细胞因子诱导的杀伤细胞(CIK)联合治疗恶性肿瘤的免疫疗效。方法选取158例晚期恶性肿瘤患者进行研究,采集患者外周血单个核细胞,贴壁细胞经IL-4、GM-CSF、TNF-α诱导,并经流式细胞仪检测证实为DC,悬浮细胞经CD3单抗、γ-干扰素、IL-2诱导,并经流式细胞仪检测证实为CIK细胞,DCs在培养的第7 d、第8 d、第9 d、第10 d分别回输给患者,CIK细胞在培养的第11 d、第12 d、第13 d、第14 d分别回输给患者,于治疗结束4 w后,应用流式细胞仪检测患者外周血T细胞亚群水平,应用酶联免疫吸附实验(enzymelinked immunosorbent assay,ELISA)法检测白细胞介素7(IL-7)、干扰素-γ(INF-γ)和白细胞介素2(IL-2)水平,以评价细胞免疫功能,同时观察治疗过程中有无不良反应发生。结果 158例恶性肿瘤患者治疗前后外周血中CD3+、CD4+、CD8+T细胞百分数和CD4+/CD8+比值差异有显著性(P<0.05);IL-2、INF-γ和IL-7水平差异有显著性(P<0.01);除27例患者出现发热外,其余患者均无明显不良反应发生。结论 DC-CIK细胞联合治疗恶性肿瘤安全有效,能提高机体免疫功能。

Objective To assess the immune efficacy of dendritic ceils （DCs） combined with cytokine induced killer（CIK） ceils on malignant tumors. Methods Peripheral blood mononu- clear cells were isolated from 158 patients with malignant tumors. The attached cells were in- duced by IL-4, GM-CSF, and TNF-α, and then confirmed as DCs by flow cytometry; the sus- pension cells were induced by CD3 monoclonal antibody, INF-γ, and IL-2, and then confirmed as CIK cells by flow cytometry. DCs were transfused back to the patients on the 7th day, 8th day, 9th day, and 10th day. CIK cells were transfused back to the patients on the llth day, 12th day, 13th day, and 14th day. After 4 weeks, lymphocyte subsets was determined by flow- cytometry; cytokine production was determined by ELISA, which reflecting the immune func- tion of patients. Adverse reactions was observed at the same time. Results The levels ofCD3 ＋, CD4 ＋, CD8 ＋ and the ratio of CD4 ＋/CD8 ＋ increased significantly compared with those before treatment（P 〈0. 05）. The levels of IL-2, INF-γ and IL-7 increased significantly com- pared with those before treatment（P 〈 0.01 ）. Except 27 cases appeared fever, the rest pa- tients had no obvious side effects. Conclusion DC-CIK cells combination therapy malignant tumor is safe and effective, and can improve immune function.