Abstract
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 H&sub2;O&sub2; 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. H&sub2;O&sub2; was abundantly produced within tumor microenvironments, and there was an inverse correlation between CD56(dim) NK cell infiltration and H&sub2;O&sub2; production. CD56(dim) NK cells are more sensitive to apoptosis induced by physiological levels of H&sub2;O&sub2; than CD56(bright) NK cells. Furthermore, the exposure of NK cells to H&sub2;O&sub2; resulted in the impairment of ADCC activity. In conclusion, H&sub2;O&sub2; 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.