Grundy Martin A, Zhang Tong, Sentman Charles L
Department of Microbiology and Immunology, Dartmouth Medical School, 6W Borwell Building, One Medical Center Drive, Lebanon, NH 03756, USA.
Cancer Immunol Immunother. 2007 Aug;56(8):1153-61. doi: 10.1007/s00262-006-0264-1. Epub 2006 Dec 8.
Natural killer (NK) cells have been shown critical in reducing tumor lung metastasis in various murine cancer models. Effector molecules such as perforin and IFN-gamma may play important roles in inhibition of metastasis. However, most of these conclusions were based on experiments that involved quantitation of metastatic colonies several weeks after tumor challenge. The roles of NK cells and their effector molecules (perforin and IFN-gamma) in the initial immune responses against tumor metastasis in lungs are still unknown. By using the B16F10 melanoma tumor model combined with confocal microscopy, we observed an increase in numbers of B16F10 cells in NK-depleted mice at 60 min post tumor inoculation, but this effect was independent of perforin or IFN-gamma. In addition, NK cell numbers in lungs after tumor injection rapidly increased suggesting a redistribution of NK cells in the lungs. However, NK cells were not found in contact with tumor cells until day 6 or later. Our data indicate that during early responses against B16F10 cells, NK cells use another mechanism(s) besides perforin and IFN-gamma to prevent tumor metastasis.
在多种小鼠癌症模型中,自然杀伤(NK)细胞已被证明在减少肿瘤肺转移方面至关重要。诸如穿孔素和干扰素-γ等效应分子可能在抑制转移中发挥重要作用。然而,这些结论大多基于肿瘤接种数周后对转移瘤集落进行定量的实验。NK细胞及其效应分子(穿孔素和干扰素-γ)在针对肺部肿瘤转移的初始免疫反应中的作用仍不清楚。通过使用B16F10黑色素瘤肿瘤模型并结合共聚焦显微镜,我们观察到在肿瘤接种后60分钟,NK细胞耗竭的小鼠中B16F10细胞数量增加,但这种效应与穿孔素或干扰素-γ无关。此外,肿瘤注射后肺中的NK细胞数量迅速增加,表明NK细胞在肺中重新分布。然而,直到第6天或更晚才发现NK细胞与肿瘤细胞接触。我们的数据表明,在针对B16F10细胞的早期反应中,NK细胞除了穿孔素和干扰素-γ之外还利用其他机制来防止肿瘤转移。