Galectin-9 expands unique macrophages exhibiting plasmacytoid dendritic cell-like phenotypes that activate NK cells in tumor-bearing mice
Galectin-9 expands unique macrophages exhibiting plasmacytoid dendritic cell-like phenotypes that activate NK cells in tumor-bearing mice
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DOI：
10.1016/j.clim.2008.09.014
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发表时间：
2009-03-01
影响因子：
8.6
通讯作者：
Hirashima, Mitsuomi
中科院分区：
文献类型：
--
作者：
Nobumoto, Atsuya;Oomizu, Souichi;Hirashima, Mitsuomi
Gatectin-9（Gat-9）通过阻断肿瘤细胞与内皮和细胞外基质的粘附来抑制肿瘤细胞的转移。在这项研究中，我们解决了Gal-9参与抗肿瘤活性。Gal-9显著延长了携带B16 F10黑素瘤的小鼠的存活。Gat-9可增加荷瘤小鼠NK细胞、CD 8 T细胞和巨噬细胞的数量。在NK细胞、巨噬细胞和CD 8 T细胞缺失的小鼠中，Gat-9介导的抗肿瘤活性并未被诱导。与PBS处理的小鼠相比，来自Gat-9处理的小鼠的NK细胞表现出显著更高的细胞溶解活性。天然NK细胞与Gat-9处理小鼠的巨噬细胞的共培养导致NK活性增强，尽管Gal-9本身并不增强NK活性。我们还发现具有浆细胞样细胞（pDC）表型（PDCA-1和B220）的Ly-6C（+）CD 11b（+）F4/80（+）巨噬细胞负责增强NK活性。这些结果提供了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的证据。(C)2008年爱思唯尔公司All rights reserved.
Gatectin-9 (Gat-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. Gat-9 increased the numbers of NK cells, CD8 T cells and macrophages in tumor-bearing mice. Gat-9-mediated anti-tumor activity was not induced in NK cell-, macrophage- and CD8 T cell-depleted mice. NK cells from Gat-9-treated mice, compared to PBS-treated mice, exhibited significantly higher cytolytic activity. Co-culture of naive NK cells with macrophages from Gat-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. (C) 2008 Elsevier Inc. All rights reserved.