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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >IL-15 has innate anti-tumor activity independent of NK and CD8 T cells.
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IL-15 has innate anti-tumor activity independent of NK and CD8 T cells.

机译：IL-15具有独立于NK和CD8 T细胞的先天性抗肿瘤活性。

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摘要

The innate immune system is crucial for host defense and immunosurveillance against pathogens and tumor cells. IL-15 is a pleiotropic cytokine with important effects on cells of the innate and adaptive immune systems. The NK cell- and CD8(+) T cell-mediated functions of IL-15 against tumor cells have been well documented. However, it has not been established whether IL-15 has innate anti-tumor functions independent of these cells. Here, we explored the innate anti-tumor potential of IL-15 using a B16F10 melanoma tumor model. IL-15tg mice exhibited significantly more resistance to tumor growth and metastasis compared to B6 mice, and to IL-15(-/-) mice, which exhibited increased susceptibility to B16F10 challenge. In vivo depletion of NK cells and CD8(+) T cells abrogated the innate resistance to B16F10 cells in B6 but not in IL-15tg mice. In addition, lung macrophages from IL-15tg mice produced significantly higher levels of NO and IL-12 compared with macrophages from B6 or IL-15(-/-) mice. To examine whether IL-15 has innate anti-tumor activity independent of NK cells and CD8(+) T cells, we developed Ad-Op-hIL-15; this resulted in significantly higher levels of biologically active hIL-15. Delivery of Ad-Op-hIL-15 into RAG-2(-/-)/gamma(c)(-/-) mice significantly suppressed tumor burden in the lungs compared with the control adenovirus vector. Our results show that IL-15 can have innate anti-tumor activity independent of NK cells and CD8(+) T cells and the common gamma(c)R.
机译：先天免疫系统对于宿主防御病原体和肿瘤细胞的防御和免疫监视至关重要。 IL-15是一种多效细胞因子，对先天和适应性免疫系统的细胞具有重要作用。 NK细胞和CD8（+）T细胞介导的IL-15对肿瘤细胞的功能已得到充分证明。但是，尚未确定IL-15是否具有独立于这些细胞的先天性抗肿瘤功能。在这里，我们使用B16F10黑色素瘤肿瘤模型探索了IL-15的先天性抗肿瘤潜力。与B6小鼠和对IL-15（-/-）小鼠相比，IL-15tg小鼠对肿瘤生长和转移的抵抗力明显更高，后者对B16F10攻击的敏感性更高。 NK细胞和CD8（+）T细胞的体内耗竭废除了B6中对B16F10细胞的固有抗性，但在IL-15tg小鼠中则没有。此外，与来自B6或IL-15（-/-）小鼠的巨噬细胞相比，来自IL-15tg小鼠的肺巨噬细胞产生的NO和IL-12水平明显更高。为了检查IL-15是否具有独立于NK细胞和CD8（+）T细胞的先天性抗肿瘤活性，我们开发了Ad-Op-hIL-15。这导致生物活性hIL-15的水平明显升高。与对照组腺病毒载体相比，将Ad-Op-hIL-15递送到RAG-2（-/-）/γ（c）（-/-）小鼠中可显着抑制肺中的肿瘤负荷。我们的结果表明，IL-15可以独立于NK细胞和CD8（+）T细胞以及常见的γ（c）R而具有先天性抗肿瘤活性。

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