IL-28 elicits antitumor responses against murine fibrosarcoma

Muneo Numasaki, Masatoshi Tagawa, Fumi Iwata, Takashi Suzuki, Akira Nakamura, Masahiro Okada, Yoichiro Iwakura, Setsuya Aiba, Mutsuo Yamaya

研究成果: Article査読

105 被引用数 (Scopus)

抄録

IL-28 is a recently described antiviral cytokine. In this study, we investigated the biological effects of IL-28 on tumor growth to evaluate its antitumor activity. IL-28 or retroviral transduction of the IL-28 gene into MCA205 cells did not affect in vitro growth, whereas in vivo growth of MCA205IL-28 was markedly suppressed along with survival advantages when compared with that of controls. When the metastatic ability of IL-28-secreting MCA205 cells was compared with that of controls, the expression of IL-28 resulted in a potent inhibition of metastases formation in the lungs. IL-28-mediated suppression of tumor growth was mostly abolished in irradiated mice, indicating that irradiation-sensitive cells, presumably immune cells, are primarily involved in the IL-28-induced suppression of tumor growth. In vivo cell depletion experiments displayed that polymorphonuclear neutrophils, NK cells, and CD8 T cells, but not CD4 T cells, play an equal role in the IL-28-mediated inhibition of in vivo tumor growth. Consistent with these findings, inoculation of MCA205IL-28 into mice evoked enhanced IFN-γ production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN-γ and is independent of IL-12, EL-17, and EL-23. IL-28 increased the total number of splenic NK cells in SCID mice and enhanced IL-12-induced IFN-γ production in vivo and expanded spleen cells in C57BL/6 mice. Moreover, IL-12 augmented IL-28-mediated antitumor activity in the presence or absence of IFN-γ. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors.

本文言語English
ページ(範囲)5086-5098
ページ数13
ジャーナルJournal of Immunology
178
8
DOI
出版ステータスPublished - 2007 4 15

ASJC Scopus subject areas

  • 免疫アレルギー学
  • 免疫学

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