Cigarette smoke impairs NK cell-dependent tumor immune surveillance
Cigarette smoke impairs NK cell-dependent tumor immune surveillance
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DOI：
10.4049/jimmunol.178.2.936
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发表时间：
2007-01-15
影响因子：
4.4
通讯作者：
Stampfli, Martin R.
中科院分区：
文献类型：
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作者：
Lu, Ling-Min;Zavitz, Caleb C. J.;Stampfli, Martin R.
在这项研究中，我们研究了香烟烟雾对肿瘤免疫监视的影响及其对小鼠肺转移模型中肺肿瘤负荷的后果。香烟烟雾暴露显著增加了B16-MO 5黑色素瘤攻击后肺转移的数量。这种影响是可逆的;我们观察到戒烟后肿瘤结节明显减少。使用RAG 2（-/-）和RAG 2（-/-）gamma（-/-）（c）小鼠，我们提供了强有力的证据，即肿瘤发生率的增加是NK细胞依赖性的。此外，我们表明，香烟烟雾抑制NK细胞活化和衰减NK细胞的CTL活性，激活或抑制受体表达没有明显的影响。最后，NK细胞通过骨髓来源的树突状细胞的激活赋予了对烟雾暴露小鼠肺转移的保护作用;然而，保护作用不如假暴露小鼠有效。据我们所知，这是第一个实验证据表明，香烟烟雾损害NK细胞依赖的肿瘤免疫监视，改变免疫与肿瘤负荷增加有关。我们的研究结果表明，先天免疫的改变可能导致吸烟者患癌症的风险增加。
In this study, we investigated the impact of cigarette smoke on tumor immune surveillance and its consequences to lung tumor burden in a murine lung metastasis model. Cigarette smoke exposure significantly increased the numbers of lung metastases following B16-MO5 melanoma challenge. This effect was reversible; we observed significantly fewer tumor nodules following smoking cessation. Using RAG2(-/-) and RAG2(-/-)gamma(-/-)(c) mice, we provide strong evidence that increased tumor incidence was NK cell dependent. Furthermore, we show that cigarette smoke suppressed NK activation and attenuated NK CTL activity, without apparent effect on activating or inhibitory receptor expression. Finally, activation of NK cells through bone marrow-derived dendritic cells conferred protection against lung metastases in smoke-exposed mice; however, protection was not as efficacious as in sham-exposed mice. To our knowledge, this is the first experimental evidence showing that cigarette smoke impairs NK cell-dependent tumor immune surveillance and that altered immunity is associated with increased tumor burden. Our findings suggest that altered innate immunity may contribute to the increased risk of cancer in smokers.