NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice.
NKT cell exacerbation of liver metastases arising from melanomas transplanted into either the eyes or spleens of mice.
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DOI：
10.1167/iovs.10-7067
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发表时间：
2011-05
影响因子：
4.4
通讯作者：
Wanhua Yang;Haochuan Li;E. Mayhew;J. Mellon;Peter W. Chen;J. Niederkorn
中科院分区：
文献类型：
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作者：
Wanhua Yang;Haochuan Li;E. Mayhew;J. Mellon;Peter W. Chen;J. Niederkorn
目的探讨自然杀伤T细胞（NKT）在眼内黑色素瘤小鼠肝转移发展中的作用。方法将来源于皮肤B16黑色素瘤细胞系（B16LS9）的细胞移植到野生型C57BL/6小鼠和nkt细胞缺陷型j - α18（-/-）和CD1d（-/-）小鼠的玻璃体或脾囊下。通过组织病理学评估肝转移的发展。通过体内抗asialo- gm1抗血清选择性清除和体外NK细胞介导的B16LS9黑色素瘤细胞溶解，研究NK细胞对肝转移的影响。通过体内和体外单克隆抗体中和检测IL-10和转化生长因子(TGF)-β在抑制肝脏NK对肝转移的抵抗中的作用。结果肝NKT细胞，尤其是I型NKT细胞，可促进眼内黑色素瘤的肝转移。nkt细胞缺陷小鼠发生的依赖nk细胞的肝转移显著减少。肿瘤诱导的肝脏NKT细胞，特别是I型NKT细胞，通过il -10依赖性过程抑制肝脏nk细胞的细胞毒性。结论NKT细胞在多种小鼠肿瘤模型中具有保护作用。然而，目前的研究结果显示，NKT细胞加剧了眼内黑色素瘤引起的肝转移。据作者所知，这是首次报道肝脏NKT细胞，特别是I型NKT细胞通过产生IL-10来抑制肝脏nk细胞的抗转移活性。这些结果表明，肝脏NKT细胞活性可能在肝转移的免疫监视中起重要作用。
PURPOSE To explore the role of natural killer T (NKT) cells in the development of liver metastases in mice harboring intraocular melanomas. METHODS Cells derived from the cutaneous B16 melanoma cell line (B16LS9) were transplanted either into the vitreous body or under the spleen capsules of wild-type C57BL/6 mice and NKT-cell-deficient Jα18(-/-) and CD1d(-/-) mice. The development of liver metastases was evaluated by histopathology. The effect of NK cells on liver metastases was determined by selective depletion with anti-asialo-GM1 antiserum in vivo and NK-cell-mediated cytolysis of B16LS9 melanoma cells in vitro. The role of IL-10 and transforming growth factor (TGF)-β in the inhibition of liver NK resistance to liver metastases was determined by in vivo and in vitro neutralization with monoclonal antibodies. RESULTS Liver NKT cells, especially type I NKT cells, enhanced liver metastases arising from intraocular melanomas. NKT-cell-deficient mice developed significantly fewer liver metastases that were NK-cell dependent. Tumor-induced liver NKT cells, especially type I NKT cells, inhibited liver NK-cell cytotoxicity by an IL-10-dependent process. CONCLUSIONS NKT cells exert protective effects in many murine tumor models. However, the present results reveal that NKT cells exacerbate liver metastases arising from intraocular melanomas. To the authors' knowledge, this is the first report that liver NKT cells, especially type I NKT cells, inhibit liver NK-cell antimetastatic activity by the production of IL-10. These results suggest that hepatic NKT cell activity can have an important effect in the immune surveillance of liver metastases.