IL-28 elicits antitumor responses against murine fibrosarcoma.
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-gamma production and cytotoxic T cell activity in spleen cells. Antitumor action of IL-28 is partially dependent on IFN-gamma 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-gamma 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-gamma. These findings indicate that IL-28 has bioactivities that induce innate and adaptive immune responses against tumors.
Numasaki
Muneo
M
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan. numasaki77@aol.com
Tagawa
Masatoshi
M
Iwata
Fumi
F
Suzuki
Takashi
T
Nakamura
Akira
A
Okada
Masahiro
M
Iwakura
Yoichiro
Y
Aiba
Setsuya
S
Yamaya
Mutsuo
M
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics* / Q000502:physiology; D005260:Female; D005354:Fibrosarcoma / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D015316:Genetic Therapy; D007371:Interferon-gamma / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018121:Receptors, Cytokine / Q000032:analysis; D012190:Retroviridae / Q000235:genetics; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D007378:Interleukins; D000095022:Interferon Lambda
D016207:Cytokines; D007371:Interferon-gamma; D018664:Interleukin-12; D018121:Receptors, Cytokine; C511668:interferon-lambda protein, mouse; D007378:Interleukins; D000095022:Interferon Lambda