The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity of NK cells in cancer patients.
The regulatory effect of UL-16 binding protein-3 expression on the cytotoxicity of NK cells in cancer patients.
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DOI：
10.1038/srep06138
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发表时间：
2014-08-20
影响因子：
4.6
通讯作者：
Mao C
中科院分区：
文献类型：
--
作者：
Mou X;Zhou Y;Jiang P;Zhou T;Jiang Q;Xu C;Liu H;Zheng T;Yuan G;Zhang Y;Chen D;Mao C
活化性免疫受体NKG2D（自然杀伤组2，成员D）及其配体在先天性和适应性免疫应答中起重要作用。UL16结合蛋白3（ULBP3）是一种NKG2D配体，在某些上皮肿瘤细胞上过表达。在这项研究中，我们研究了ULBP3表达对自然杀伤（NK）细胞的细胞毒活性的影响。通过流式细胞术分析、免疫组织化学和时间分辨荧光免疫分析来测量ULBP3。乳酸脱氢酶释放法测定NK细胞的杀伤活性。我们发现ULBP3在肿瘤细胞系和肿瘤组织中过表达。来自癌症患者而非健康供体的血清含有升高水平的可溶性ULBP3（sULBP3）。重要的是，ULBP3在肿瘤细胞表面的高表达增强了NKG2D介导的NK细胞的细胞毒性。然而，低水平的sULBP3（<15 ng/ml）通过降低NK细胞上的NKG2D表达而减弱NK细胞的细胞毒性。 进一步分析显示，来自大多数癌症患者（> 70%）的血清样品含有低水平的sULBP 3。我们的研究结果表明，肿瘤细胞表达表面和可溶性ULBP3，其调节NK细胞活性。因此，ULBP3是一个潜在的治疗靶点，用于改善针对癌症的免疫应答。
The activating immunoreceptor NKG2D (natural killer group 2, member D) and its ligands play important roles in the innate and adaptive immune responses. UL16-binding protein 3 (ULBP3), an NKG2D ligand, is overexpressed on certain epithelial tumor cells. In this study, we investigated the effect of ULBP3 expression on the cytotoxic activity of natural killer (NK) cells. ULBP3 were measured by flow cytometry analysis, immunohistochemistry, and time-resolved fluoroimmunoassay. The cytotoxicity of NK cells was determined with the lactate dehydrogenase release assay. We found that ULBP3 was overexpressed on tumor cell lines and tumor tissues. Serum from cancer patients, but not from healthy donors, contained elevated levels of soluble ULBP3 (sULBP3). Importantly, high expression of ULBP3 on the cell surface of tumor cells augmented NKG2D-mediated NK cell cytotoxicity. However, low levels of sULBP3 (<15 ng/ml) weakened the cytotoxicity of NK cells by decreasing NKG2D expression on NK cells. Further analysis showed that serum samples from most cancer patients (>70%) contained the low level of sULBP3. Our results demonstrate that tumor cells express surface and soluble ULBP3, which regulate NK cell activity. Thus, ULBP3 is a potential therapeutic target for improving the immune response against cancer.