Interleukin-18 and the costimulatory molecule B7-1 have a synergistic anti-tumor effect on murine melanoma; implication of combined immunotherapy for poorly immunogenic malignancy

Daeho Cho, Tai Gyu Kim, Wangjae Lee, Young Il Hwang, Hyun Il Cho, Hoon Han, Ohchan Kwon, Daejin Kim, Hyunjeong Park, Dong Houh

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Interleukin-18 has been described recently as a cytokine secreted primarily by Kupffer cells. Furthermore, it has been shown that it has significant anti-tumor effects, which are mediated by T cells and natural killer cells, in a manner similar to interleukin-12. Here, we report the evaluation of the effects of the systemic administration of interleukin-18 in combination with B7-1 (CD80) expressed on tumor cells [interleukin-18 + B7-1] on the growth of murine B16 melanoma in vivo. After the subcutaneous inoculation of B16 melanoma, B16 tumors grew progressively in immunocompetent syngeneic C57BL/6 mice. Mice treated with either interleukin-18 or immunized with B7-1-transduced B16 did not demonstrate significant anti-tumor effect. The combination of the two treatments, however, resulted in dramatic suppression of melanoma formation, tumor growth, and a significant improvement in survival. Inhibitory effects of [interleukin-18 + B7-1] on lung metastasis in mice were also detected. Additionally, mice treated with [interleukin-18 + B7-1] showed an increase of natural killer cytotoxicity and interferon-γ production in vivo. Unlike [interleukin-18 + B7-1], [interleukin-12 + B7-1] did not have a strong antitumor effect against B16 melanoma. Histologic characterization after the [interleukin-18 + B7-1] treatment confirmed the infiltration of natural killer cells into the tumor, suggesting that natural killer cells may be involved in the [interleukin-18 + B7-1]-induced anti-tumor effect. This finding was confirmed by showing that depletion of NK1.1+ cells before immunization inhibits the [interleukin-18 + B7-1]-induced anti-tumor effect. Depletion of CD3+ cells in vivo also decreased the anti-tumor effect of [interleukin-18 + B7-1], suggesting the importance of CD3+ T cells. Collectively, combination with interleukin-18 and B7-1 expression has synergistic anti-tumor effects against B16 murine melanoma.

Original languageEnglish
Pages (from-to)928-934
Number of pages7
JournalJournal of Investigative Dermatology
Volume114
Issue number5
DOIs
Publication statusPublished - 2000 Jan 1

Keywords

  • Anti-tumor effect
  • B7-1
  • Immunotherapy
  • Interleukin-18
  • Melanoma

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

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