TCR基因多样性评估肝细胞癌患者免疫力的临床研究  

Clinical study on evaluating the immunity in patients with hepatocellular carcinoma by TCR gene diversity

作　　者：刘星 王磊石 李鲁平[2] 吴威[1] 权冬梅 吕呈 段明郁 朱梓兆 宋冠男 王岩[1] LIU Xing;WANG Leishi;LI Luping;WU Wei;QUAN Dongmei;LV Cheng;DUAN Yuming;ZHU Zizhao;SONG Guannan;WANG Yan(Diagnosis and treatment center of hepatocellular carcinoma,The Sixth People's Hospital of Shenyang,Shenyang,Liaoning,China,110006;Clinical Laboratory,The Sixth People’s Hospital of Shenyang,Liaoning,China,110006;Clinical chemistry laboratory,Shenyang Beichuang laboratory Co.Ltd,Shenyang,Liaoning,China,110117)

机构地区：[1]沈阳市第六人民医院肝癌诊治中心,辽宁沈阳110006 [2]沈阳市第六人民医院检验科,辽宁沈阳110006 [3]沈阳北创医学检验所有限公司临床化学实验室,辽宁沈阳110006

出　　处：《分子诊断与治疗杂志》2023年第2期290-293,297,共5页Journal of Molecular Diagnostics and Therapy

基　　金：沈阳市科学技术计划项目(20-205-4-038)。

摘　　要：目的 探讨特异性T细胞受体(TCR)基因的多样性对原发性肝细胞癌患者免疫力水平的评估。方法 4例原发性肝细胞癌患者采用抗PD-1单克隆抗体HX008联合贝伐珠单抗或仑伐替尼治疗,分别于患者治疗前和治疗后对外周血中的TCR进行高通量基因测序,同时进行血常规、凝血系列、肝功、肾功、离子、血糖、AFP、心肌酶谱以CT检查,监测不良事件的发生。结果 两例患者治疗后出现免疫力升高,治疗前、后免疫力健康值分别为0.029767(差)、0.126303(良)和0.044906(差)、0.132530(良),最大TCR克隆占比分别为29.76%,9.85%和1.62%,2.63%。两例患者治疗后出现免疫力降低,治疗前、后免疫力健康值分别为0.107826(良)、0.178684(优)和0.067897(中)、0.169535(优),最大TCR克隆占比分别为3.48%、2.72%和5.15%、3.56%。结论 TCR基因的多样性可以客观准确地评估原发性肝癌患者的免疫状态、机体对疾病与治疗的反应,为开发新的免疫治疗靶点以及预后监测指标提供实验基础及研究依据。Objective To investigate the effect of TCR gene diversity on the immune level of patients with primary hepatocellular carcinoma. Methods Four patients with primary hepatocellular carcinoma were treated with anti-PD-1 monoclonal antibody HX008 combined with bevacizumab or lenvatinib.High-throughput gene sequencing was performed for TCR in peripheral blood before and after treatment. Blood routine test,coagulation,liver function,renal function,ions,blood glucose,AFP,myocardial enzyme spectrum and CT scan were examined,the occurrence of adverse events after treatment was also monitored.Results Two patients had increased immunity,The immune health values before and after treatment were0.029767(poor),0.126303(good)and 0.044906(poor),0.132530(good)respectively. The proportion of the maximum TCR clone were 29.76%,9.85% and 1.62%,2.63% respectively. Two patients had decreased immunity. The immune health values before and after treatment were 0.107826(good),0.178684(excellent)and 0.067897(medium),0.169535(excellent)respectively. The proportion of the maximum TCR clone were3.48%,2.72% and 5.15%,3.56% respectively. Conclusion The diversity of TCR gene can objectively and accurately evaluate the immune status of patients with primary hepatocellular carcinoma and the body’s response to disease and treatment,and provide experimental and research basis for developing new immunotherapy targets and prognostic monitoring indicators.

关 键 词：TCR 多样性 肝细胞癌 免疫力 

分 类 号：R735.7[医药卫生—肿瘤]