原发性肝癌患者亲环素B特异性T细胞反应研究  

The study of Cyp B specific T cell response in hepatocellular carcinoma

作　　者：赵艳[1] 覃岭[2] 王熠[1] 孙焕芹[2] 李宁[3] 张永宏[2] 

机构地区：[1]首都医科大学附属北京佑安医院临检中心,100069 [2]首都医科大学附属北京佑安医院生物医学信息中心,100069 [3]首都医科大学附属北京佑安医院肝胆外科,100069

出　　处：《北京医学》2015年第9期854-856,共3页Beijing Medical Journal

基　　金：国家国际科技合作专项(2012DFA30850);北京市科技项目(D131100005313004;D131100005313005);首都卫生发展专项(首发2011-1011-02;首发2011-2018-06)

摘　　要：目的探讨亲环素B（CypB）特异性T细胞反应强度变化在原发性肝癌患者中意义。方法以北京佑安医院收治的107例HBV相关肝病患者为研究对象，分为慢性肝炎组（49例）、肝硬化组（22例）及肝癌组（36例）。采集患者外周血并分离外周血单个核细胞。采用体外合成CypB全序列多肽技术，运用ELISPOT方法分析107例患者外周血单个核细胞对CypB合成肽的细胞反应情况。结果慢性肝炎、肝硬化、肝癌患者CypB特异性T细胞反应强度分别为0[0—0]SFU／10^9PBMCs、0[0～0]SFU／10^9PBMCs及20[0—60]SFU／10^6PBMCs，3组比较差异有统计学意义（P=0．0210）；3组反应频率分别为18．4％（9／49）、18．2％（4／22）及47．2％（17／36），差异有统计学意义（P=0．071）。CypB90～208氨基酸肽段诱导的T细胞反应强度高于1～107氨基酸肽段[（34．3±5．3）SFU／10^6 PBMCsVS．（70．0±11．0）SFU／10^6PBMCs]，差异有统计学意义（t=2．922，P=0．0064）。生存分析显示，CypB特异性T细胞反应阴性组肿瘤复发率明显高于CypB特异性T细胞反应阳性组（P=0．0492）。结论肝癌患者外周血中存在CypB特异性T细胞反应，可能成为肝癌预警标志物和未来肝癌免疫治疗的新靶点。Objective To study the significance of Cyp B specific T cell response in patients with hepatocellular carcinoma （HCC）. Methods One hundred and seven patients with HBV associated liver diseases were enrolled into the study in Beijng You＇ an hospital. Patients were divided into 3 groups： chronic hepatitis B group （49 cases）, cirrhosis group （22 cases） and hepatocellular carcinoma group （36 cases）. Peripheral blood was collected and peripheral blood mononucle- ar cells were isolated. The Cyp B overlapping peptides were synthetized and peptides pools were developed. The IFN-gam- ma released elispot assay was employed to detect the Cyp B specific T cell. Results The magnitudes of Cyp B specific T cell response were calculated in patients with chronic hepatitis B infection, liver cirrhosis and HCC as 0[0-0]SFU/ 10^6PBMCs, 0[0-0]SFU/10^6pBMCs, and 20[0-60] SFU/10^6PBMCs respectively, and the difference was significant（P = 0.0210）. The recognized frequency ofCyp B in the 3 groups was 18.4%（9/49）, 18.2%（4/22）, and 47.2%（17/36）, respective- ly. The difference was significant（P = 0.0071）. The magnitude of specific T cell response inducing Cyp B peptides aa 90- 208 was （70.0±11.0）SFU/10^6pBMCs, higher than that induced by Cyp B peptides aa 1-107 （34.3±5.3）SFU/10^6PBMCs（P = 0.0064）. The analysis of relapse rate after interventional therapy was performed by survival analysis, the cumulated tumor relapse rate was significantly higher in patients without Cyp B specific T cell response than those with Cyp B specific T cell response（P = 0.0492）. Conclusion A broad Cyp B specific T cell response is found in HCC patients, which can be improved by interventional therapy. Cyp B specific T cell response might play a role in antitumor growth and will be a new target for immune therapy in the future.

关 键 词：原发性肝癌 亲环素B 细胞免疫 介入治疗 

分 类 号：R735.7[医药卫生—肿瘤]