Nobumoto Atsuya, Oomizu Souichi, Arikawa Tomohiro, Katoh Shigeki, Nagahara Keiko, Miyake Minoru, Nishi Nozomu, Takeshita Keisuke, Niki Toshiro, Yamauchi Akira, Hirashima Mitsuomi
Department of Immunology and Immunopathology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Clin Immunol. 2009 Mar;130(3):322-30. doi: 10.1016/j.clim.2008.09.014. Epub 2008 Oct 29.
Galectin-9 (Gal-9) inhibits the metastasis of tumor cells by blocking their adhesion to endothelium and the extracellular matrix. In this study, we addressed the involvement of Gal-9 in anti-tumor activity. Gal-9 significantly prolonged the survival of B16F10 melanoma-bearing mice. Gal-9 increased the numbers of NK cells, CD8 T cells and macrophages in tumor-bearing mice. Gal-9-mediated anti-tumor activity was not induced in NK cell-, macrophage- and CD8 T cell-depleted mice. NK cells from Gal-9-treated mice, compared to PBS-treated mice, exhibited significantly higher cytolytic activity. Co-culture of naïve NK cells with macrophages from Gal-9-treated mice resulted in enhanced NK activity, although Gal-9 itself did not enhance the NK activity. We also found that Ly-6C(+)CD11b(+)F4/80(+) macrophages with plasmacytoid cell (pDC)-like phenotypes (PDCA-1 and B220) were responsible for the enhanced NK activity. These results provide evidence that Gal-9 promotes NK cell-mediated anti-tumor activity by expanding unique macrophages with a pDC-like phenotype.
半乳糖凝集素-9（Gal-9）通过阻断肿瘤细胞与内皮细胞及细胞外基质的黏附来抑制肿瘤细胞的转移。在本研究中，我们探讨了Gal-9在抗肿瘤活性中的作用。Gal-9显著延长了荷B16F10黑色素瘤小鼠的生存期。Gal-9增加了荷瘤小鼠体内自然杀伤（NK）细胞、CD8 T细胞和巨噬细胞的数量。在NK细胞、巨噬细胞和CD8 T细胞耗竭的小鼠中未诱导出Gal-9介导的抗肿瘤活性。与经磷酸盐缓冲盐水（PBS）处理的小鼠相比，经Gal-9处理的小鼠的NK细胞表现出显著更高的细胞溶解活性。尽管Gal-9本身并未增强NK活性，但将未成熟NK细胞与经Gal-9处理的小鼠的巨噬细胞共培养可增强NK活性。我们还发现，具有浆细胞样细胞（pDC）样表型（PDCA-1和B220）的Ly-6C(+)CD11b(+)F4/80(+)巨噬细胞是NK活性增强的原因。这些结果证明，Gal-9通过扩增具有pDC样表型的独特巨噬细胞来促进NK细胞介导的抗肿瘤活性。
