原著

著者

Hide KANEDA, Marimo SATO*, Yoko NANGO, Takeshi KUSAFUKA and Hideaki TAHARA*
Division of Pediatric Surgery, Department of Surgery, Nihon University School of Medicine
*Department of Surgery and Bioengineering, Advanced Clinical Research Center,
Institute of Medical Science, The University of Tokyo

要旨

Co-administration of a-galactosylceramide (a-GalCer) with Interleukin (IL)-12 augmented the anti-metastaticeffects of either treatment alone in mice. This treatment was associated with the elevation of natural killer (NK)activity though the increase of interferon (IFN)-g activity. IL-23 is a relatively novel cytokine, which consists of aheterodimer of the IL-12p40 subunit and a novel p19 subunit. IL-23 has biological activities similar to but distinctfrom IL-12. IL-23 can enhance the proliferation of memory T cells and the production of IFN-g, IL-12, and tumornecrosis factor (TNF)-a from activated CD4+ T-cells. IL-23 is produced by dendritic cells and possesses potentanti-tumor and anti-metastatic activity in murine tumor models. We investigated the combined therapeutic effect ofIL-23 and a-GalCer against highly metastatic B16F10 melanoma. This combinetion treatment of tumor-bearingmice induced an elevation of the serum IFN-g concentration at a much lower dose compared with the IL-12 treatmentalone. IFN-g production was observed in CD4+ and CD8 + T-cells in the lymph nodes obtained from thesemice upon stimulation with immobilized anti-CD3 mAb. In parallel with the augmented IFN-g production, thetumor-specific cytotoxic and NK activities were significantly augmented with the combined therapy. Furthermore,lymph nodes cells cultured with anti-CD3 mAb alone, or with a-GalCer and anti-CD3 mAb, produced high levelsof IFN-g and IL-17. These findings suggest that the combination treatment using IL-23 and a-GalCer may activateboth NKT cells and NK cells, and may have potent anti-metastatic effects.

keyword

Interleukin-23 (IL-23), a-galactosylceramide (a-GalCer), immunotherapy, Natural Killer (NK) T
cells, lung metastasis