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

Daisuke Nobuoka, Yutaka Motomura, Hirofumi Shirakawa, Toshiaki Yoshikawa, Toshimitsu Kuronuma, Mari Takahashi, Kohei Nakachi, Hiroshi Ishii, Junji Furuse, Naoto Gotohda, Shinichiro Takahashi, Toshio Nakagohri, Masaru Konishi, Taira Kinoshita, Hiroyuki Komori, Hideo Baba, Toshiyoshi Fujiwara, Tetsuya Nakatsura

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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 chemoembolization (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.

Original languageEnglish
Pages (from-to)63-70
Number of pages8
JournalInternational journal of oncology
Volume40
Issue number1
DOIs
Publication statusPublished - Jan 1 2012

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Keywords

  • Cytotoxic T lymphocyte
  • Glypican-3
  • Hepatocellular carcinoma
  • Immunotherapy
  • Radiofrequency ablation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Nobuoka, D., Motomura, Y., Shirakawa, H., Yoshikawa, T., Kuronuma, T., Takahashi, M., Nakachi, K., Ishii, H., Furuse, J., Gotohda, N., Takahashi, S., Nakagohri, T., Konishi, M., Kinoshita, T., Komori, H., Baba, H., Fujiwara, T., & Nakatsura, T. (2012). Radiofrequency ablation for hepatocellular carcinoma induces glypican-3 peptide-specific cytotoxic T lymphocytes. International journal of oncology, 40(1), 63-70. https://doi.org/10.3892/ijo.2011.1202