First Department of Surgery, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi 409-3898, Japan.
Cancer Immunol Immunother. 2011 Dec;60(12):1801-10. doi: 10.1007/s00262-011-1082-7. Epub 2011 Aug 3.
Human NK cells can be divided into two subsets, CD56(dim)CD16(+)NK and CD56(bright)CD16(-)NK cells, based on their expression of CD56 and CD16. In the present study, we analyzed the relationship between CD56(dim)/CD56(bright) NK cells and H₂O₂ in tumor-infiltrating NK cells in patients with gastric (n = 50) and esophageal (n = 35) cancer. The ratio of CD56(dim) NK cells infiltrating tumors gradually decreased according to disease progression. H₂O₂ was abundantly produced within tumor microenvironments, and there was an inverse correlation between CD56(dim) NK cell infiltration and H₂O₂ production. CD56(dim) NK cells are more sensitive to apoptosis induced by physiological levels of H₂O₂ than CD56(bright) NK cells. Furthermore, the exposure of NK cells to H₂O₂ resulted in the impairment of ADCC activity. In conclusion, H₂O₂ produced within tumor microenvironments inversely correlated with the infiltration of CD56(dim) NK cells, possibly due to their preferentially induced cell death. These observations may explain one of the mechanisms behind NK cell dysfunction frequently observed in tumor microenvironments.
基于 CD56 和 CD16 的表达，人类 NK 细胞可分为两个亚群，即 CD56(dim)CD16(+)NK 和 CD56(bright)CD16(-)NK 细胞。本研究分析了 50 例胃癌和 35 例食管癌患者肿瘤浸润 NK 细胞中 CD56(dim)/CD56(bright)NK 细胞与 H₂O₂之间的关系。肿瘤浸润的 CD56(dim)NK 细胞的比例随着疾病进展逐渐降低。H₂O₂在肿瘤微环境中大量产生，CD56(dim)NK 细胞浸润与 H₂O₂产生呈负相关。与 CD56(bright)NK 细胞相比，CD56(dim)NK 细胞对生理水平的 H₂O₂诱导的细胞凋亡更为敏感。此外，NK 细胞暴露于 H₂O₂会导致 ADCC 活性受损。总之，肿瘤微环境中产生的 H₂O₂与 CD56(dim)NK 细胞的浸润呈负相关，可能是由于它们优先诱导细胞死亡。这些观察结果可能解释了 NK 细胞在肿瘤微环境中经常观察到的功能障碍的机制之一。
