肺癌患者淋巴结内培养CIK细胞的抑瘤实验和临床前期研究  

Anti-tumor activities of CIK cells derived from lymph nodes of lung cancer patients

作　　者：滕家俊[1] 周严[1] 刘显勋 韩宝惠[1] 钟华[1] 

机构地区：[1]上海市胸科医院呼吸内科,上海200030

出　　处：《中国癌症杂志》2015年第9期665-670,共6页China Oncology

基　　金：上海市科委引导课题(124119a6300);上海市胸科医院重大重点项目(2014YZDC20700)

摘　　要：背景与目的:细胞因子诱导的杀伤细胞(cytokine-induced killer cells,CIK)兼具T淋巴细胞强大的杀瘤活性与自然杀伤细胞(natural killer cell,NK)杀瘤的非MHC限制性。CIK细胞可直接杀伤肿瘤细胞,调节并增强免疫功能,同时不损害机体免疫环境,其在治疗恶性肿瘤中的作用已得到广泛认可。本研究旨在观察肺癌手术患者淋巴结培养获得的CIK细胞的杀瘤活性及其临床应用的安全性。方法:获取上海市胸科医院6例经手术治疗的非小细胞肺癌患者的淋巴结及外周血,体外培养分别获得CIK细胞。通过倒置显微镜观察两组CIK细胞的形态,检测淋巴结组及外周血组CIK细胞表型,应用CCK8显色法检测两组CIK细胞对A549细胞株的抗增殖作用,观察回输后血液中癌胚抗原(carcino-embryonic antigen,CEA)的变化及其临床应用中的不良反应。结果:淋巴结组和外周血组CIK细胞CD3^+CD56+T细胞的比例均>30%。不同效靶比淋巴结组CIK细胞对A549细胞的抑制率均高于外周血组(P<0.05)。回输淋巴结内CIK细胞后肺癌患者有不同程度CEA下降。不良反应轻微,主要表现为皮疹和发热。结论:肺癌手术患者的淋巴结可用于培养CIK细胞,其活性优于外周血来源的CIK细胞,临床前期实验证实安全性高。Background and purpose： Cytokine-induced killer （CIK） has both the advantages of T lympho- cytes＇ powerful anti-tumor activity and NK ceils＇ tumor killing capacity without MHC restriction. It could directly kill tumor cells, regulate and enhance immune function, without damaging the structure and functions of the immune sys- tem. Its effects on the treatment of malignant solid tumors has been widely recognized. This study aimed to evaluate the anti-proliferation effects of CIK cells obtained and cultivated from hmg cancer patients＇ lymph nodes. Meanwhile, the safety of clinical transfusion was observed. Methods： The peripheral blood and lymph nodes of 6 surgery patients with lung cancer from Shanghai Chest Hospital were used to cultivate CIK cells for 14 days. The phenotypes of CIK cells were detected by flow cytometry. The anti-proliferation activities of CIK cells on A549 lung cancer cells were detected by CCK8 assay. The morphological changes of CIK cells were observed by invert microscope. The expression of CEA level and adverse events were evaluated after CIK transfusion. Results： The proportion of CD3＋CD56＋T lymphocyte in two groups were both more than 30%. The CCK8 assay showed that the suppression rate of lymph nodes group was higher than that of peripheral blood group at each effect/target ratio（P〈0.05）. The adverse effect of CIK transfusion was mild and tolerable. The expression of CEA level decreased in patients. Conclusion： Lymph nodes of surgery patients with lung cancer can be used for cultivation of CIK cells. The anti-tumor activity of CIK isolated from lymph nodes is better than that of CIK cells cultivated from peripheral blood. Preclinical experiments showed high safety.

关 键 词：肺癌 淋巴结 免疫治疗 

分 类 号：R734.2[医药卫生—肿瘤]