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* Department of Geriatric and Respiratory Medicine,
Department of Anatomic Pathology, and
Department of Dermatology, Tohoku University School of Medicine, Sendai, Japan;
Department of Pathology, Chiba Cancer Center Research Institute, Chiba, Japan;
¶ Laboratory of Marine Biochemistry, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan;
|| Department of Experimental Immunology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan;
# Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan; and
** Center for Experimental Medicine, Institute of Medical Science, University of Tokyo, Tokyo, Japan
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-
production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN- and is independent of IL-12, IL-17, and IL-23. IL-28 increased the total number of splenic NK cells in SCID mice and enhanced IL-12-induced IFN- 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-. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Address correspondence and reprint requests to Dr. Muneo Numasaki, Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, Japan. E-mail address: numasaki77{at}aol.com
2 Abbreviations used in this paper: KO, knockout; CM, complete medium.
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  N. Ank, M. B. Iversen, C. Bartholdy, P. Staeheli, R. Hartmann, U. B. Jensen, F. Dagnaes-Hansen, A. R. Thomsen, Z. Chen, H. Haugen, et al. An Important Role for Type III Interferon (IFN-{lambda}/IL-28) in TLR-Induced Antiviral Activity J. Immunol., February 15, 2008; 180(4): 2474 - 2485. [Abstract] [Full Text] [PDF]
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