First Department of Surgery, University of Yamanashi, Yamanashi, Japan.
Dis Esophagus. 2010 Nov;23(8):675-81. doi: 10.1111/j.1442-2050.2010.01073.x.
NK cells can be divided into two subsets, CD56(dim) and CD56(bright) NK cells, based on their expression of CD56 and CD16. In the present study, we analyzed NK cell dysfunction in patients with esophageal squamous cell carcinoma (ESCC), with a particular focus on the expression of CD16 and CD56 molecules. Expression of CD16 and CD56, and the distribution of CD56(dim) or CD56(bright) NK cells gated on CD56(+)CD3(-) NK cells were compared between ESCC patients (n= 40) and healthy donors (n= 38). Purified NK cells were evaluated for Cetuximab-mediated antibody-dependent cellular cytotoxicity (ADCC) against epidermal growth factor receptor (EGFR)-expressing ESCC cell lines. Although there were no significant differences in the distribution of CD56(dim) and CD56(bright) NK cells between ESCC patients and healthy donors, down-regulated CD16 and up-regulated CD56 were significantly observed on NK cells of ESCC patients, paralleling the impairment of Cetuximab-mediated ADCC, in comparison with healthy donors. After patients received curative resections of ESCC, the down-regulated CD16 and up-regulated CD56 were significantly restored to the levels of healthy donors. Moreover, TGF-beta1 partially contributed to down-regulation of CD16 on NK cells. Down-regulated CD16 and up-regulated CD56 molecules on NK cells were observed in ESCC patients, resulting in NK cell dysfunction.
NK 细胞可以根据其 CD56 和 CD16 的表达分为两个亚群，即 CD56(dim) 和 CD56(bright) NK 细胞。在本研究中，我们分析了食管鳞状细胞癌（ESCC）患者 NK 细胞功能障碍，特别关注 CD16 和 CD56 分子的表达。比较了 40 例 ESCC 患者和 38 例健康供者之间 CD56(+)CD3(-)NK 细胞上 CD16 和 CD56 表达以及 CD56(dim)或 CD56(bright)NK 细胞的分布。对纯化的 NK 细胞进行了西妥昔单抗介导的针对表达表皮生长因子受体（EGFR）的 ESCC 细胞系的抗体依赖性细胞毒性（ADCC）的评价。尽管 ESCC 患者和健康供者之间 CD56(dim)和 CD56(bright)NK 细胞的分布没有差异，但与健康供者相比，ESCC 患者 NK 细胞上 CD16 下调和 CD56 上调显著，与西妥昔单抗介导的 ADCC 受损平行。ESCC 患者接受根治性切除术治疗后，下调的 CD16 和上调的 CD56 明显恢复到健康供者的水平。此外，TGF-β1 部分导致 NK 细胞上 CD16 的下调。在 ESCC 患者中观察到 NK 细胞上 CD16 下调和 CD56 上调，导致 NK 细胞功能障碍。
