摘要
背景与目的:程序性死亡[蛋白]-1(programmed death-1,PD-1)在调节外周免疫耐受中发挥重要作用,PD-1在肝细胞癌(hepatocellular carcinoma,HCC)肿瘤浸润淋巴细胞中的表达状态与效应细胞CD8^(+)T淋巴细胞的关系尚不清楚,探讨HCC肿瘤浸润淋巴细胞中PD-1的表达及预后意义。方法:收集2008年1月—2016年12月在南通市第三人民医院接受手术的344例HCC患者的病理样本,制备组织芯片;采用免疫组织化学法检测HCC组织中PD-1、程序性死亡[蛋白]配体-1(programmed death ligand-1,PD-L1)的表达,分析PD-1在肿瘤浸润淋巴细胞中的表达与HCC临床病理学参数、PD-L1的表达、CD8^(+)T淋巴细胞之间的相关性及与患者预后的关系;采用免疫组织化学双标记法检测CD8^(+)PD-1^(+)双阳性T淋巴细胞密度对HCC患者预后的影响。结果:PD-1阳性信号定位于HCC肿瘤浸润淋巴细胞的细胞膜或细胞质中。PD-1的高表达率为43.9%,其高表达与肿瘤组织学分级(P=0.009)、肿瘤细胞中PD-L1的表达(P<0.001)、肿瘤浸润淋巴细胞中PD-L1的表达(P<0.001)及肿瘤浸润CD8^(+)T淋巴细胞密度(P=0.003)有关,并且PD-1高表达是评估总生存(overall survival,OS)率、无病生存(disease-free survival,DFS)率的独立危险因子(OS:HR=1.654,P=0.010;DFS:HR=2.518,P<0.001)。另外,高密度肿瘤浸润CD8^(+)PD-1^(+)双阳性T淋巴细胞组较低密度组OS和DFS更差(P均<0.001)。结论:PD-1在HCC肿瘤浸润淋巴细胞中表达可能是潜在的预后因子。
Background and purpose:Programmed death 1(PD-1)plays an important role in the regulation of peripheral immune tolerance.The expression of PD-1 in tumor-infiltrating lymphocytes of hepatocellular carcinoma(HCC)and the relationship between PD-1 expression and CD8^(+)T lymphocytes is unclear.This study was aimed to investigate the expression of PD-1 in tumor-infiltrating lymphocytes of HCC and its prognostic significance.Methods:Pathological paraffin samples of 344 HCC patients who underwent surgery in Nantong Third People’s Hospital from January 2008 to December 2016 were included.Tissue microarray was prepared.The protein expressions of PD-1 and programmed death ligand-1(PD-L1)in HCC tissues were detected by immunohistochemical assay.Statistical analysis was performed to determine the correlation between the expression of PD-1 in tumor-infiltrating lymphocytes and the clinicopathological parameters of HCC,the expression of PD-L1,CD8^(+)T lymphocytes and the prognosis of patients.The influence of CD8^(+)PD-1^(+)double expression T lymphocyte density on the prognosis of HCC patients was detected by immunohistochemical double labeling.Results:PD-1 positive signal was localized on the membrane or cytoplasm of HCC tumor-infiltrating lymphocytes.The high expression rate of PD-1 was 43.9%,which was related to tumor histological grade(P=0.009),tumor cell PD-L1 expression(P<0.001),tumor-infiltrating lymphocytes PD-L1 expression(P<0.001)and tumor infiltrating CD8^(+)T lymphocyte density(P=0.003).Moreover,PD-1 overexpression was an independent risk factor for evaluating the overall survival(OS)rate and the disease-free survival(DFS)rate(OS:HR=1.654,P=0.010;DFS:HR=2.518,P<0.001).In addition,patients with high-density tumor-infiltrating CD8^(+)PD-1^(+)double expression T-lymphocytes had worse OS and DFS compared with those with low-density tumor(P<0.001).Conclusion:The expression of PD-1 in tumor-infiltrating lymphocytes of HCC may be a potential prognostic factor.
作者
肖锋
肖静文
邵建国
陈丽燕
顾春燕
XIAO Feng;XIAO Jingwen;SHAO Jianguo;CHEN Liyan;GU Chunyan(Department of Pathology,the Third People’s Hospital of Nantong,Affiliated Nantong Third Hospital of Nantong University,Nantong 226006,Jiangsu Province,China;Department of Gastroenterology,the Third People’s Hospital of Nantong,Affiliated Nantong Third Hospital of Nantong University,Nantong 226006,Jiangsu Province,China)
出处
《中国癌症杂志》
CAS
CSCD
北大核心
2021年第5期419-427,共9页
China Oncology
基金
南通市市级科技计划项目(JCZ18046)
南通市卫生和计划生育委员会科研课题专项(MA2019010,MB2020031)。
