Increased PD-1 and decreased CD28 expression in chronic hepatitis B patients with advanced hepatocellular carcinoma

Authors

  • Ping-Ning Hsu,

    1. Graduate Institute of Immunology, College of Medicine, National Taiwan University, Taipei, Taiwan
    2. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
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    • *Contributed equally.

  • Tsuey-Ching Yang,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
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    • *Contributed equally.

  • Jung-Ta Kao,

    1. Department of Internal Medicine, College of Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
    2. Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan
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    • *Contributed equally.

  • Ken-Sheng Cheng,

    1. Department of Internal Medicine, College of Medicine, China Medical University Hospital and China Medical University, Taichung, Taiwan
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  • Yi-Ju Lee,

    1. Institute of Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
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  • Yuan-Min Wang,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
    2. Graduate Institute of Biotechnology, National Chung Hsing University, Taichung, Taiwan
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  • Chin-Tung Hsieh,

    1. Department of Pediatrics, Lotung Poh-Ai hospital, I-Lan, Taiwan
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  • Cheng-Wen Lin,

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
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  • Yi-Ying Wu

    1. Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, Taichung, Taiwan
    2. Graduate Institute of Clinical Medical Science, China Medical University and Hospital, Taichung, Taiwan
    3. Institute of Microbiology and Immunology, College of Medicine, Chung Shan Medical University, Taichung, Taiwan
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Correspondence
Yi-Ying Wu, PhD, Department of Medical Laboratory Science and Biotechnology, China Medical University and Hospital, No. 91, Hsueh-Shih Rd., Taichung 404, Taiwan
Tel:+886 4 22053366x7228
Fax:+886 4 22057414
e-mail: yyw@mail.cmu.edu.tw

Abstract

Background/aims: Hepatitis B infection is a well-known cause of hepatocellular carcinoma (HCC). This study aims to investigate the role that the co-stimulatory molecule CD28 and co-inhibitory molecule programmed death-1 (PD-1) play in compromising the function of tumour-infiltrating lymphocytes (TIL) in hepatitis B virus (HBV)-related HCC.

Methods: A total of 45 patients with HBV-related HCC were enrolled during the period February 2008 to March 2010. The immune phenotype and the expression of PD-1, CD28 and CD127 in TIL in biopsy specimens and in peripheral blood lymphocytes (PBL) from the same patients were analysed by flow cytometry.

Results: Among the 45 patients, there was a male predominance (80%) and the mean age was 50 ± 13.68 years (range: 29–71). The majority of TIL were CD45RO+CD69+. PD-1 expression was higher and CD28 and CD127 expression levels were lower in TIL than in PBL. The prevalence of portal vein thrombosis was 40%. Furthermore, tumour thrombosis invasion into the portal vein correlated with the expression level of the PD-1 co-inhibitory molecule.

Conclusion: PD-1+ tumour-infiltrating lymphocytes correlate with portal vein thrombosis and might serve as a potential prognostic marker of and a novel therapeutic target for HBV-related HCC.

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