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5×108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. Vγ9Vδ2 T cells which passed quality control were reinfused. The dose of reinfused cells was 5×108 cells per 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 and γδT 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.

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）