Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance

Role of trans-cellular IL-15 presentation in the activation of NK cell-mediated killing, which leads to enhanced tumor immunosurveillance
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DOI：
10.1182/blood-2003-12-4187
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发表时间：
2005-01-15
期刊：
BLOOD
影响因子：
20.3
通讯作者：
Tagaya, Y
Tagaya, Y
中科院分区：
医学1区
文献类型：
--
作者：
Kobayashi, H;Dubois, S;Tagaya, Y

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白介素 15 (IL-15) 是自然杀伤 (NK) 和 CD8 T 细胞增殖和激活的关键因素。最近，我们证明单核细胞/树突状细胞上表达的IL-15Rα通过细胞与细胞接触捕获IL-15并将其反式呈递给邻近细胞（IL-15的反式呈递）。在当前的研究中，我们提供的证据表明，以反式形式存在的 IL-15（而非生理浓度下的可溶性 IL-15）可增强 NK 细胞在体外介导的杀伤活性。此外，将 IL-15Rα 转染到结肠癌细胞系 (MC38) 中，使这些细胞能够将 IL-15 反式呈递给 NK 细胞，并增强其杀伤活性。导致 NK 细胞在体外有效裂解 MC38 细胞。此外。这些转染的 MC38 细胞不再在小鼠体内形成致命的肺转移。研究还表明，在这种情况下，NK 细胞在 MC38 细胞的排斥反应中发挥着重要作用。这些结果共同表明 IL-15 反式呈递机制在体内发挥作用以增强肿瘤免疫监视机制。此外。我们的观察为预防癌症发展/转移的新策略提供了科学基础。
Interleukin 15 (IL-15) is a critical factor for the proliferation and activation of natural killer (NK) and CD8 T cells. Recently, we demonstrated that IL-15Ralpha expressed on monocytes/dendritic cells captures and presents IL-15 to neighboring cells in trans (trans-presentation of IL-15) through cell-cell contact. In the current study, we provide evidence that the IL-15 presented in trans, but not soluble IL-15 at physiologic concentrations, augments the killing activity mediated by NK cells in vitro. In addition, transfection of IL-15Ralpha into a colon carcinoma cell line (MC38) enabled these cells to present IL-15 in trans to NK cells and augmented their killing activity. resulting in the efficient lysis of MC38 cells by NK cells in vitro. Furthermore. these transfected MC38 cells no longer form fatal pulmonary metastases in mice. It was also shown that NK cells play an important role in the rejection of MC38 cells under these circumstances. These results collectively suggest that the IL-15 trans-presentation mechanism operates in vivo to augment the tumor immune surveillance mechanism. Furthermore. our observation provides the scientific basis for a novel strategy to prevent cancer development/metastasis.