Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.
Interleukin-21 can efficiently restore impaired antibody-dependent cell-mediated cytotoxicity in patients with oesophageal squamous cell carcinoma.
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DOI：
10.1038/sj.bjc.6605502
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发表时间：
2010-02-02
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
我们之前报道过，由于 NK 细胞功能障碍，与健康供体相比，癌症患者中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) 受到损害。在本研究中，我们评估了 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 IL-21 存在的情况下检查了曲妥珠单抗和西妥昔单抗介导的外周血单核细胞 (PBMC) 或来自 ESCC 患者 (n=20) 和健康供体 (n=16) 的富集 NK 细胞的 ADCC。我们进一步分析了 NK 细胞上针对 IL-21 的 ADCC 相关分子（穿孔素、颗粒酶 B 和 CD247）。添加IL-21以剂量依赖性方式增强曲妥珠单抗和西妥昔单抗介导的PBMC或富集NK细胞的ADCC，并且与健康供体相比，患者中IL-21增强的ADCC水平足够高，与NK细胞上CD247的上调平行。 IL-21可以通过上调CD247分子有效恢复ESCC患者受损的ADCC。
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.
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影响因子：
64.8
作者：
Fan, QR;Mosyak, L;Wiley, DC
通讯作者：
Wiley, DC
影响因子：
64.8
作者：
Parrish-Novak, J;Dillon, SR;Foster, D
通讯作者：
Foster, D
影响因子：
8.4
作者：
Hall, Peter S.;Cameron, David A.
通讯作者：
Cameron, David A.
影响因子：
4.4
作者：
Asao, H;Okuyama, C;Sugamura, K
通讯作者：
Sugamura, K
影响因子：
6.4
作者：
Hanawa, M;Suzuki, S;Ooi, A
通讯作者：
Ooi, A