Interleukin-33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development
Interleukin-33 activates and recruits natural killer cells to inhibit pulmonary metastatic cancer development
复制标题
Interleukin-33 激活并招募自然杀伤细胞以抑制肺转移癌的发展
DOI：
10.1002/ijc.32779
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发表时间：
2019-12-05
影响因子：
6.4
通讯作者：
Fang, Fang
中科院分区：
文献类型：
--
作者：
Qi, Lu;Zhang, Qiuyan;Fang, Fang
越来越多的证据表明IL-33在调节肿瘤发展中起重要作用。然而，从许多研究中获得的相互矛盾的结果突出了IL-33的不同功能。IL-33调节肿瘤发展的详细机制值得进一步研究。在这里，我们报告说，IL-33管理可以有效地抑制小鼠乳腺癌肺转移的发展。在我们的模型中，IL-33促进巨噬细胞产生TNF-α，这增加了自然杀伤（NK）细胞上的IL-33特异性受体（ST 2）表达，并且在IL-33诱导的NK细胞活化中至关重要。IL-33治疗还促进嗜酸性粒细胞和CD 8（+）T细胞在肺中产生CCL 5，其介导NK细胞向肿瘤微环境的募集。NK细胞的全身激活和局部募集导致肺部强烈的肿瘤排斥反应。我们的研究报告了IL-33介导的转移性肿瘤抑制的新机制，并为靶向转移性肿瘤提供了潜在的治疗策略。
Increasing evidence suggests that IL-33 plays an important role in regulating tumor development. However, conflicting results, obtained from numerous studies, have highlighted the divergent functions of IL-33. The detailed mechanisms by which IL-33 modulates tumor development merit further investigation. Here, we report that IL-33 administration can effectively inhibit the development of pulmonary metastasis of breast cancer in a mouse. In our model, IL-33 promotes the production of TNF-alpha by macrophages, which increases IL-33 specific receptor (ST2) expression on natural killer (NK) cells and is pivotal in IL-33-induced NK cell activation. IL-33 treatment also facilitates the production of CCL5 in the lung by eosinophils and CD8(+) T cells, which mediates the recruitment of NK cells to the tumor microenvironment. The systemic activation and local recruitment of NK cells result in potent tumor rejection in the lung. Our study reports a novel mechanism for the IL-33-meditated suppression of metastatic cancer and provides potential therapeutic strategies for targeting metastatic tumor.