First Department of Surgery, University of Yamanashi, Yamanashi 409-3898, Japan.
Br J Cancer. 2010 Feb 2;102(3):520-9. doi: 10.1038/sj.bjc.6605502. Epub 2009 Dec 22.
We previously reported that Trastuzumab- and Cetuximab-mediated antibody-dependent cell-mediated cytotoxicity (ADCC) in cancer patients was impaired in comparison with that in healthy donors because of NK-cell dysfunction. In this study, we evaluated whether IL-21 could improve the impairment of ADCC in patients with oesophageal squamous cell carcinoma (ESCC), as IL-21 was reported to have the ability to activate NK cells.
We examined Trastuzumab- and Cetuximab-mediated ADCC of peripheral blood mononuclear cells (PBMCs) or of enriched NK cells derived from ESCC patients (n=20) and healthy donors (n=16) in the presence of IL-21. We further analysed ADCC-related molecules (perforin, granzyme-B, and CD247) on NK cells in response to IL-21.
Trastuzumab- and Cetuximab-mediated ADCC of PBMCs or of enriched NK cells was enhanced by the addition of IL-21 in a dose-dependent manner and the levels of ADCC enhanced by IL-21 in patients were high enough in comparison with those in healthy donors, paralleling the upregulation of CD247 on NK cells.
IL-21 could efficiently restore impaired ADCC in ESCC patients with the upregulation of CD247 molecules.
我们之前报道过，由于 NK 细胞功能障碍，与健康供体相比，癌症患者曲妥珠单抗和西妥昔单抗介导的抗体依赖性细胞介导的细胞毒性（ADCC）受损。在这项研究中，我们评估了白细胞介素 21（IL-21）是否可以改善食管鳞状细胞癌（ESCC）患者的 ADCC 损伤，因为据报道 IL-21 具有激活 NK 细胞的能力。
我们在白细胞介素 21 的存在下检查了来自 ESCC 患者（n=20）和健康供体（n=16）的外周血单核细胞（PBMC）或富集 NK 细胞的曲妥珠单抗和西妥昔单抗介导的 ADCC。我们进一步分析了 NK 细胞对白细胞介素 21 的 ADCC 相关分子（穿孔素、颗粒酶 B 和 CD247）。
IL-21 以剂量依赖性方式增强了 PBMC 或富集 NK 细胞的曲妥珠单抗和西妥昔单抗介导的 ADCC，并且与健康供体相比，IL-21 增强的 ADCC 水平在患者中足够高，与 NK 细胞上 CD247 的上调相平行。
IL-21 可以通过上调 CD247 分子有效地恢复 ESCC 患者受损的 ADCC。
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