低Tim-3表达水平与肝癌氩氦刀冷冻消融联合TACE治疗响应的相关性  

Correlation Between Low Tim-3 Expression Level and Response to Argon Helium Knife Cryoablation Combined with TACE Treatment in Hepatocellular Carcinoma

作　　者：张剑[1] 杨荟玉[2] 张自森[1] 王利娟[1] 张红巧[1] 郭彦伟 ZHANG Jian;YANG Huiyu;ZHANG Zisen(The Fifth Affiliated Hospital of Zhengzhou University,Zhengzhou,450052)

机构地区：[1]郑州大学第五附属医院,450052 [2]郑州大学第一附属医院,450052

出　　处：《实用癌症杂志》2023年第2期235-239,共5页The Practical Journal of Cancer

基　　金：河南省卫健委,省部共建重点项目(编号:SBGJ202002063);河南省医学科技攻关计划联合共建项目(编号:2018020256)。

摘　　要：目的探讨肝癌浸润免疫细胞中Tim-3表达含量与氩氦刀冷冻消融(AHCS)联合肝动脉化疗栓塞术(TACE)治疗响应以及预后的相关性。方法使用免疫组化方法检测肿瘤活检组织免疫细胞中Tim-3表达水平。Tim-3高表达被定义为TILs上的染色>5%,依据Tim-3表达情况将患者分为Tim-3低表达组、Tim-3高表达组。2组患者均接受AHCS-TACE联合治疗。为期3年的随访,观察指标包括总生存期(OS),肿瘤进展时间(TTP)以及客观反应率(ORR)。治疗3月后应用ELISA试验方法检测患者CD_(4)^(+)、CD_(8)^(+)、CD_(4)^(+)/CD_(8)^(+)T淋巴细胞亚群水平。结果2组患者在性别、ECOG评分、Child-Pugh分级、肿瘤大小、AFP水平、有无门静脉侵犯相关指标均无统计学差异。经AHCS-TACE联合治疗后,Tim-3低表达组患者的ORR显著高于Tim-3高表达组。Tim-3低表达组的中位OS为27.07月,Tim-3高表达组为19.79个月,差异具有统计学意义(P<0.05)。Tim-3低表达组的中位TTP为16.41个月,而Tim-3高表达组为11.49个月。Tim-3低表达组患者的CD_(4)^(+)、CD_(8)^(+)、CD_(4)^(+)/CD_(8)^(+)T细胞水平均显著高于Tim-3高表达组患者。多因素分析显示,有无门静脉瘤栓和肝内肿瘤的最大直径以及Tim-3表达含量是OS和TTP的预后因素。结论肿瘤浸润免疫细胞中Tim-3含量对TACE+AHCS联合治疗患者预后具有预测价值。基于Tim-3的高表达模式,应用Tim-3的免疫检查点抑制剂进行维持治疗,可能会改善接受AHCS-TACE联合治疗的患者的预后和完全反应率。Objective To investigate the correlation between the level of Tim-3 expression in hepatocellular carcinoma infiltrating immune cells and the response to treatment with argon helium knife cryoablation(AHCS)combined with hepatic artery chemoembolization(TACE)and the prognosis.Methods Immunohistochemistry was used to detect Tim-3 expression in immune cells from tumour biopsies.high Tim-3 expression was defined as>5%staining on TILs,and patients were divided into a low Tim-3 expression group and a high Tim-3 expression group based on Tim-3 expression,both groups received AHCS-TACE combination therapy.Patients in both groups were treated with the combination of AHCS-TACE and were followed up for 3 years for overall survival(OS),time to tumour progression(TTP)and objective response rate(ORR).Patients’CD_(4)^(+),CD_(8)^(+)and CD_(4)^(+)/CD_(8)^(+)T-lymphocyte subsets were measured by ELISA after 3 months of treatment.Results There had no statistical difference in gender,ECOG score,Child-Pugh stage,tumor size,AFP level,and whether had portal vein invasion between the 2 groups.After AHCS-TACE combination therapy,the ORR of patients in the Tim-3 low expression group was significantly higher than that in the Tim-3 high expression group,and the median OS was 27.07 months in the Tim-3 low expression group and 19 months in the Tim-3 high expression group The median TTP was 16.41 months in the Tim-3 low expression group compared to 11.49 months in the Tim-3 high expression group.patients in the Tim-3 low expression group had significantly higher levels of CD_(4)^(+),CD_(8)^(+)andCD_(4)^(+)/CD_(8)^(+)T cells than those in the Tim-3 high expression group.patients.Multifactorial analysis showed that the presence or absence of portal vein tumour thrombus and the maximum diameter of the intrahepatic tumour,as well as the level of Tim-3 expression,were prognostic factors for OS and TTP.Conclusion The level of Tim-3 in tumour-infiltrating immune cells is predictive of prognosis in patients treated with the combination of TACE+AHCS.B

关 键 词：Tim-3表达水平 氩氦刀冷冻消融 TACE 治疗响应 预后 

分 类 号：R735.7[医药卫生—肿瘤]