Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes

Int J Oncol. 2012 Jan;40(1):63-70. doi: 10.3892/ijo.2011.1202. Epub 2011 Sep 15.


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.

Publication types

  • Case Reports
  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Carcinoma, Hepatocellular / immunology*
  • Carcinoma, Hepatocellular / surgery*
  • Catheter Ablation*
  • Epitopes, T-Lymphocyte / immunology
  • Female
  • Glypicans / immunology*
  • HLA-A2 Antigen / genetics
  • HLA-A2 Antigen / immunology
  • HLA-A24 Antigen / genetics
  • HLA-A24 Antigen / immunology
  • Humans
  • Liver Neoplasms / immunology*
  • Liver Neoplasms / surgery*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Prospective Studies
  • T-Lymphocytes, Cytotoxic / immunology*


  • Epitopes, T-Lymphocyte
  • GPC3 protein, human
  • Glypicans
  • HLA-A2 Antigen
  • HLA-A24 Antigen