title: Radiofrequency ablation for hepatocellular carcinoma induces glypican-3             peptide-specific cytotoxic T lymphocytes.
abstract: Glypican-3 (GPC3), a carcinoembryonic antigen, is an ideal target for anticancer             immunotherapy against hepatocellular carcinoma (HCC). In this study, we attempted             to compare the induction of the GPC3-specific T-cell-mediated immune response             after locoregional therapies in HCC patients and tumor-bearing mice. Twenty-seven             HCC patients treated with locoregional therapies, including radiofrequency ablation             (RFA), surgical resection and transcatheter arterial chemo-embolization (TACE),             were prospectively enrolled in this study. Additionally, we performed RFA experiments             using a mouse model. GPC3-specific T-cell response was investigated pre-treatment             and post-treatment by an interferon-γ enzyme-linked immunospot assay using peripheral             blood mononuclear cells from HCC patients and lymph node cells from tumor-bearing             mice. Circulating GPC3-specific cytotoxic T lymphocytes (CTLs) were increased             in 5 of 9 patients after RFA and in 4 of 9 patients after TACE, but in only 1             of 9 patients after surgical resection. All 7 patients with GPC3-expressing HCCs             exhibited an increase in GPC3-specific CTLs after RFA or TACE, whereas none of             the 7 patients did after surgical resection. The number of increased GPC3-specific             CTLs after RFA was significantly larger than that after surgical resection (P=0.023).             Similarly, the frequency of GPC3-specific CTLs after RFA was significantly greater             than that after surgical resection in the mouse model (P=0.049). We validated             for the first time the stronger effect on the immune system brought by RFA compared             with surgical resection for HCC patients and tumor-bearing mice. Combined treatment             of RFA and immunotherapy is a reasonable strategy against HCC.
authors.affiliation: Section for Cancer Immunotherapy, Investigative Treatment Division,                     Research Center for Innovative Oncology, National Cancer Center Hospital                     East, 6-5-1 Kashiwanoha, Kashiwa, Chiba 277-8577, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nobuoka
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: Toshimitsu
authors.initials: T
authors.lastname: Kuronuma
authors.forename: Mari
authors.initials: M
authors.lastname: Takahashi
authors.forename: Kohei
authors.initials: K
authors.lastname: Nakachi
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Junji
authors.initials: J
authors.lastname: Furuse
authors.forename: Naoto
authors.initials: N
authors.lastname: Gotohda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakagohri
authors.forename: Masaru
authors.initials: M
authors.lastname: Konishi
authors.forename: Taira
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Komori
authors.forename: Hideo
authors.initials: H
authors.lastname: Baba
authors.forename: Toshiyoshi
authors.initials: T
authors.lastname: Fujiwara
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology* / Q000601:surgery*; D017115:Catheter Ablation; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D053673:Glypicans / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000235:genetics / Q000276:immunology; D059871:HLA-A24 Antigen / Q000235:genetics / Q000276:immunology; D006801:Humans; D008113:Liver Neoplasms / Q000276:immunology* / Q000601:surgery*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D011446:Prospective Studies; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
chemical_list: D018984:Epitopes, T-Lymphocyte; C105937:GPC3 protein, human; D053673:Glypicans; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen