Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jul 28, 2011; 17(28): 3322-3329
Published online Jul 28, 2011. doi: 10.3748/wjg.v17.i28.3322
Immunostaining of PD-1/PD-Ls in liver tissues of patients with hepatitis and hepatocellular carcinoma
Bao-Ju Wang, Jun-Jie Bao, Jun-Zhong Wang, Yang Wang, Min Jiang, Ming-You Xing, Wan-Guang Zhang, Jun-Ying Qi, Michael Roggendorf, Meng-Ji Lu, Dong-Liang Yang
Bao-Ju Wang, Jun-Jie Bao, Jun-Zhong Wang, Yang Wang, Dong-Liang Yang, Division of Clinical Immunology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Jun-Jie Bao, Department of Clinical Laboratory, Guangzhou Women and Children’s Medical Center, Guangzhou 510055, Guangdong Province, China
Min Jiang, Meng-Ji Lu, Department of Microbiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430015, Hubei Province, China
Ming-You Xing, Jun-Ying Qi, Department of Infectious Disease, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Wan-Guang Zhang, Hepatic Surgery Center, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Michael Roggendorf, Meng-Ji Lu, Institute of Virology, University Hospital Essen, Hufelandstrasse 55, 45122 Essen, Germany
Author contributions: Wang BJ and Bao JJ performed the experiments and data analysis; Wang JZ and Wang Y performed the experiments; Xing MY, Zhang WG and Qi JY contributed to collecting the samples and providing the patients information; Wang BJ, Roggendorf M, Lu MJ and Yang DL contributed to research designation, manuscript preparation and editing.
Supported by Grants from the National Mega Research Program of China, No. 2008ZX10002-011; the National Key Basic Research Program of China, No. 2001CB510008, 2005CB522901, 2007CB512804 and 2009CB522500; the Deutsche Forschungsgemeinschaft (SFB/Transregio 60)
Correspondence to: Dong-Liang Yang, MD, Professor of Medicine, Director, Division of Clinical Immunology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Jiefang Avenue 1095, Wuhan 430030, Hubei Province, China. dlyang@tjh.tjmu.edu.cn
Telephone: +86-27-83662894 Fax: +86-27-83662894
Received: September 16, 2010
Revised: November 13, 2010
Accepted: November 20, 2010
Published online: July 28, 2011
Abstract

AIM: To investigate the expression of programmed death (PD)-1, PD ligand 1 (PD-L1) and PD-L2 in liver tissues in the context of chronic hepatitis and hepatocellular carcinoma (HCC).

METHODS: Liver biopsies and HCC specimens from patients were collected and histologically examined. The expression of PD-1, PD-L1, and PD-L2 in biopsy specimens of chronic hepatitis and HCC specimens was evaluated by immunohistochemical staining. The association between the expression level of PD-1, PD-L1, and PD-L2 and clinical and pathological variables was analyzed statistically.

RESULTS: Expression of PD-1 was found in liver-infiltrating lymphocytes. In contrast, PD-L1 and PD-L2 were expressed in non-parenchyma liver cells and tumor cells. The expression of PD-L1 was significantly correlated with hepatitis B virus infection (1.42 ± 1.165 vs 0.50 ± 0.756, P = 0.047) and with the stage of HCC (7.50 ± 2.121 vs 1.75 ± 1.500 vs 3.00 ± 0.001, P = 0.018). PD-1 and PD-Ls were significantly up-regulated in HCC specimens (1.40 ± 1.536 vs 5.71 ± 4.051, P = 0.000; 1.05 ± 1.099 vs 4.29 ± 3.885, P = 0.004; 1.80 ± 1.473 vs 3.81 ± 3.400, P = 0.020).

CONCLUSION: PD-L1 may contribute to negative regulation of the immune response in chronic hepatitis B. PD-1 and PD-Ls may play a role in immune evasion of tumors.

Keywords: Hepatitis B virus; Programmed death-1; Programmed death ligands; Hepatitis; Hepatocellular carcinoma