PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性

doi:10.19401/j.cnki.1007-3639.2021.05.008

中国癌症杂志 ›› 2021, Vol. 31 ›› Issue (5): 419-427.doi: 10.19401/j.cnki.1007-3639.2021.05.008

PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性

肖　锋 ¹ ，肖静文¹ ，邵建国 ² ，陈丽燕 ¹ ，顾春燕 ¹

1. 南通大学附属南通第三医院，南通市第三人民医院病理科，江苏南通 226006 ；
2. 南通大学附属南通第三医院，南通市第三人民医院消化科，江苏南通 226006

出版日期:2021-05-30 发布日期:2021-05-31
通信作者: 顾春燕 E-mail: guchunyan143@aliyun.com
基金资助:
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）。

The expression of programmed death 1 in tumor-infiltrating lymphocytes of hepatocellular carcinoma and its correlation with prognosis

XIAO Feng ¹ , XIAO Jingwen ¹, SHAO Jianguo ², CHEN Liyan ¹, GU Chunyan¹

1. Department of Pathology, the Third People’s Hospital of Nantong, Affiliated Nantong Third Hospital of Nantong University, Nantong 226006, Jiangsu Province, China; 2. Department of Gastroenterology, the Third People’s Hospital of Nantong, Affiliated Nantong Third Hospital of Nantong University, Nantong 226006, Jiangsu Province, China

Published:2021-05-30 Online:2021-05-31
Contact: GU Chunyan E-mail: guchunyan143@aliyun.com

摘要/Abstract

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。

关键词: 程序性死亡［蛋白］-1, 程序性死亡［蛋白］配体-1, 肝细胞癌, 预后

Abstract: 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.

Key words: Programmed death 1, Programmed death ligand-1, Hepatocellular carcinoma, Prognosis

肖　锋, 肖静文, 邵建国, 陈丽燕, 顾春燕 . PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性[J]. 中国癌症杂志, 2021, 31(5): 419-427.

XIAO Feng , XIAO Jingwen , SHAO Jianguo , CHEN Liyan , GU Chunyan . The expression of programmed death 1 in tumor-infiltrating lymphocytes of hepatocellular carcinoma and its correlation with prognosis[J]. China Oncology, 2021, 31(5): 419-427.

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PD-1在肝细胞癌肿瘤浸润淋巴细胞中的表达及与预后的相关性

The expression of programmed death 1 in tumor-infiltrating lymphocytes of hepatocellular carcinoma and its correlation with prognosis

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