肿瘤细胞表面NK细胞配体的表达及其对NK-92细胞的敏感性  

Expression of NK Ligands in Tumor Cell Lines and Their Sensitivity to NK-92

作　　者：朱慧芬[1] 黄宏[2] 符明鹏 郭子龙 雷萍[1] 沈关心[1] 何勇 Zhu Huifen;Huang Hong;Fu Mingpeng(Department of Immunology,School of Basic Medical Science,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China;Department of Respiratory and Critical Care Medicine,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院基础医学院免疫学系,武汉430030 [2]华中科技大学同济医学院附属同济医院呼吸与危重医学科,武汉430030 [3]武汉大学中南医院核医学科,武汉430071

出　　处：《华中科技大学学报（医学版）》2018年第4期383-387,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.31570937)

摘　　要：目的分析肿瘤细胞表面NK细胞配体的表达及其对NK-92细胞的敏感性,以期获得对不同肿瘤的最佳治疗效果。方法采用半定量RT-PCR方法,测定8种肿瘤细胞(K562、Raji、U937、Molt-4、Jurkat、HepG2、Hela、PC3)的9种NK配体(MICA、MICB、ULBP1、ULBP2、CD58、Nectin-2、CD155、LLT-1、HLA-E)。通过羧基荧光素二醋酸盐琥珀酰亚胺酯(CFSE)和碘化丙啶(PI)双标记测定NK-92细胞对这些肿瘤细胞的杀伤活性。结果根据肿瘤细胞对NK-92的敏感性将肿瘤细胞分为两组(敏感组和中度敏感组),K562、Raji、U937、Molt-4对NK-92细胞敏感性高,Jurkat、HepG2、Hela、PC3对NK-92细胞中度敏感。CD58和HLA-E的转录水平在两组之间的差异具有统计学意义(P值分别为0.002和0.006),CD58的表达在敏感组高于中度敏感组,而HLA-E的表达在敏感组低于中度敏感组。结论 CD58hi或HLAElow的肿瘤细胞对NK-92的杀伤作用更敏感,因此,肿瘤细胞CD58和HLA-E的表达测定可以作为临床NK细胞治疗的肿瘤检测标志。Objective To optimize their efficacy as an immunotherapy for different malignancies,the association between NK ligands＇ expression and susceptibility of malignancies to NK-92 was analyzed.Methods Nine representative NK ligands（MICA,MICB,ULBP1,ULBP2,CD58,Nectin-2,CD155,LLT-1 and HLA-E）in 8 tumor cell lines（K562,Raji,U937,Molt-4,Jurkat,HepG2,Hela and PC3）were detected by semi-quantitative RT-PCR.Susceptibility of malignancies to NK-92 was analyzed by flow cytometry using CFSE and PI double staining.Results Tumor cell lines were classified into two groups（sensitive group and moderately sensitive group）according to their susceptibility to NK-92 cytotoxicity.K562,Raji,U937 and Molt-4 were sensitive to NK-92 cytotoxicity,and Jurkat,HepG2,Hela and PC3 were moderately sensitive.The transcriptional levels of CD58 and HLA-E showed statistical differences between the two groups（P=0.002 and 0.006,respectively）.CD58 expression in sensitive group was elevated while HLA-E was decreased compared with moderately sensitive group.Conclusion Our preliminary study showed CD58 and HLA-E expression on tumor cells could be detected to evaluate the susceptibility of a malignancy to clinical NK-92 treatment.

关 键 词：NK-92细胞 肿瘤细胞系 NK激活性受体 NK抑制性受体 细胞毒性 

分 类 号：R73-351[医药卫生—肿瘤]