title: Detection of glypican-3-specific CTLs in chronic hepatitis and liver cirrhosis.
abstract: Glypican-3 (GPC3) is one of carcinoembryonic antigens known to be overexpressed in hepatocellular carcinoma (HCC). It has been suggested that GPC3 may be related to the development of HCC in a background of chronic hepatitis (CH) and liver cirrhosis (LC). Therefore, in an attempt to establish an early diagnostic marker of HCC, we quantified the number of GPC3-specific CTLs in the peripheral blood of CH and LC patients. We selected CH and LC patients who were HCV-RNA (+) or HBs antigen (+) within 6 months prior to the study and had no HCC nodules as detected by imaging. A total of 56 patients with CH and LC, and 45 patients with HLA-A24+ or HLA-A2+ were enrolled for this investigation. After isolation of mononuclear cells from each patient's peripheral blood specimens, we performed ELISPOT assay using HLA-A24- and HLA-A2-restricted GPC3 peptides. In the ELISPOT assay, GPC3-specific CTLs were detected in 10 of the 45 CH and LC cases (22%). In addition, the plasma titers of anti-GPC3 IgG were increased in the CH and LC patients as compared with those in healthy donors. GPC3-specific CTLs were found to be present not only in patients with HCC, but also in patients with CH and LC. This suggests the possibility of GPC3-specific CTLs serving as a marker for the early diagnosis of imaging-invisible HCC.
authors.affiliation: Section for Cancer Immunotherapy, Investigative Treatment Division, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Chiba, Japan. ehayashi@east.ncc.go.jp
authors.forename: Emiko
authors.initials: E
authors.lastname: Hayashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Motomura
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shirakawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Oba
authors.forename: Shuta
authors.initials: S
authors.lastname: Nishinakagawa
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kojima
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomura
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D001323:Autoantibodies / Q000097:blood*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000821:virology; D003602:Cytotoxicity, Immunologic; D055088:Early Detection of Cancer; D004797:Enzyme-Linked Immunosorbent Assay; D053673:Glypicans / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D019694:Hepatitis B, Chronic / Q000150:complications / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000150:complications / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D020014:K562 Cells; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology*; D008113:Liver Neoplasms / Q000276:immunology / Q000821:virology; D018655:Lymphocyte Count; D011237:Predictive Value of Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D001323:Autoantibodies; C105937:GPC3 protein, human; D053673:Glypicans; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007074:Immunoglobulin G