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Clin Immunol. 2008 Dec;129(3):428-37. doi: 10.1016/j.clim.2008.08.012. Epub 2008 Sep 27.

Functional impairment in circulating and intrahepatic NK cells and relative mechanism in hepatocellular carcinoma patients.

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Institute of Microbiology, Chinese Academy of Sciences, Beijing 100012, China.


Functional defects in natural killer (NK) cells have been proposed to be responsible for the failure of anti-tumor immune responses. Whether and how NK cells are impaired in hepatocellular carcinoma (HCC) patients remain unknown. In this study, we found that HCC patients displayed a dramatic reduction in peripheral CD56(dim)CD16(pos) NK subsets compared with healthy subjects. A significant reduction of CD56(dim)CD16(pos) NK subsets was also found in tumor regions compared with non-tumor regions in the livers of these HCC patients. Both these peripheral and tumor-infiltrating NK cells exhibited poorer capacity to produce IFN-gamma and kill K562 targets, which was further found to be associated with increased CD4(+)CD25(+) T regulatory cells as we previously-described in HCC patients. Addition of Tregs from HCC patients efficiently inhibited the anti-tumor ability of autologous NK cells in vitro. These findings are helpful for understanding the mechanism of NK cell-mediated anti-tumor immune responses in HCC patients.

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