同种异体γδT细胞免疫疗法治疗晚期肝细胞癌的安全性及其对患者免疫功能的影响  

Safety of allogeneic γδT cell immunotherapy for advanced hepatocellular carcinoma and its effect on patients'immune function

作　　者：陈彦 张亦甜 徐艳 李曼 黎嘉伟 孟令雯 向征[4] 刘冰 尹芝南 吴斌[1] CHEN Yan;ZHANG Yitian;XU Yan;LI Man;LI Jiawei;MENG Lingwen;XIANG Zheng;LIU Bing;YIN Zhinan;WU Bin(Department of Gastroenterology,the Third Affiliated Hospital of Sun Yat-Sen University,Guangzhou 510630,Guangdong,China;Department of Interventional Medicine&Zhuhai Interventional Medical Centre,Zhuhai People’s Hospital,Zhuhai 519000,Guangdong,China;Biomedical Translational Research Institute,Jinan University,Guangzhou 510632,Guangdong,China;Department of Microbiology and Immunology,School of Medicine,Jinan University,Guangzhou 510632,Guangdong,China)

机构地区：[1]中山大学附属第三医院消化内科,广东广州510630 [2]珠海市人民医院介入医学科暨珠海市介入诊疗中心,广东珠海519000 [3]暨南大学生物医学转化研究院,广东广州510632 [4]暨南大学基础医学与公共卫生学院微生物学与免疫学系,广东广州510632

出　　处：《中国肿瘤生物治疗杂志》2024年第3期253-260,共8页Chinese Journal of Cancer Biotherapy

基　　金：国家自然科学基金面上项目(No.31570898);广东省自然科学基金项目(No.2016A030313112);广东省基础与应用基础研究基金项目(No.2020A1515111203)。

摘　　要：目的:探讨使用同种异体Vγ9Vδ2 T细胞回输治疗晚期肝细胞癌(HCC)患者的安全性及治疗后患者免疫功能的变化。方法:选择2021年10月至2022年10月珠海市人民医院收治的4例晚期HCC患者,从健康供体获取外周血单个核细胞(PBMC)后经刺激扩增培养获得Vγ9Vδ2 T细胞,经质控放行后予以回输治疗,回输细胞剂量为5×10^(8)个/次,每两周一次,回输次数9次以上,治疗后检测患者αβT细胞、B细胞、NK细胞、γδT细胞各亚群比例,转氨酶、肌酐、肌酸激酶等肝、肾、心功能生化标志物,以及血常规三系(白细胞系统、红细胞系统和血小板系统)细胞数量的变化。结果:4例患者在回输治疗后均显示出对异体Vγ9Vδ2 T细胞良好的耐受性;转氨酶、肌酐、肌酸激酶等肝、肾、心功能生化标志物以及血常规三系细胞数量在回输前后均无明显变化;患者的Tfh1、Tc1、CD127^(+)TEM、HLADR^(+)CD8^(+)T细胞、CD27-B细胞比例有升高趋势,提示特异性免疫功能的增强。结论:同种异体Vγ9Vδ2 T细胞治疗晚期HCC有较好的安全性并可在一定程度上改善患者的免疫功能。Objective:To investigate the safety of allogeneic Vγ9Vδ2 T cell reinfusion therapy for advanced hepatocellular carcinoma(HCC)and the changes in the immune function of patients after treatment.Methods:Four advanced HCC patients admitted into Zhuhai People’s Hospital between October,2021 and October,2022 were selected for the study.Peripheral blood mononuclear cells(PBMC)were obtained from healthy donors and Vγ9Vδ2 T cells were obtained after stimulation and amplification of PBMC.Vγ9Vδ2T cells which passed quality control were reinfused.The dose of reinfused cell swas 5×10^(8)cellsper time,once every two weeks,and reinfusions were carried out for more than 9 times.After treatments,the proportions of subgroup cells(αβT cells,B cells,NK cells andγδT cells)were detected.Biochemical markers of liver,kidney and heart function,such as transaminase,creatinine and creatine kinase were detected.Changes in the number of three types of cells in blood routine(the leukocyte system,the red blood cell system,and the platelet system)were detected.Results:After reinfusion treatment,all four patients showed good tolerance to allogeneic Vγ9Vδ2 T cells.Their biochemical markers of liver,kidney and heart functions,such as transaminase,creatinine and creatine kinase and the cell counts of three types of cells in blood routine showed no significant difference before and after reinfusion.Proportions of Tfh1,Tc1,CD127^(+)TEM,HLADR^(+)CD8^(+)T cells,CD27-B cells increased,which indicated the enhancement of specific immunity.Conclusion:Allogeneic Vγ9Vδ2 T cell therapy for advanced HCC exhibits a good safety profile and can,to a certain extent,boost the patient's immune function.

关 键 词：肝细胞癌 同种异体γδT细胞 免疫治疗 安全性 免疫功能评估 

分 类 号：R737.33[医药卫生—肿瘤] R730.2[医药卫生—临床医学] R73-37