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Open AccessArticle

Cytotoxicity of Human Hepatic Intrasinusoidal CD56bright Natural Killer Cells against Hepatocellular Carcinoma Cells

1
Division of Liver Transplantation and Hepatobiliary Surgery, Department of Surgery, University of Ulsan College of Medicine, Seoul 05505, Korea
2
Department of Convergence Medicine & Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Korea
*
Authors to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(7), 1564; https://doi.org/10.3390/ijms20071564
Received: 19 March 2019 / Revised: 26 March 2019 / Accepted: 26 March 2019 / Published: 28 March 2019
(This article belongs to the Special Issue Natural Killer and NKT Cells)
Hepatic intrasinusoidal (HI) natural killer (NK) cells from liver perfusate have unique features that are similar to those of liver-resident NK cells. Previously, we have reported that HI CD56bright NK cells effectively degranulate against SNU398 hepatocellular carcinoma (HCC) cells. Thus, the aim of this study was to further investigate the phenotype and function of HI NK cells. We found that HI CD56bright NK cells degranulated much less to Huh7 cells. HI CD56bright NK cells expressed NKG2D, NKp46, TNF-related apoptosis-inducing ligand (TRAIL), and FAS ligand (FASL) at higher levels than CD56dim cells. SNU398 cells expressed more NKG2D ligands and FAS and less PD-L1 than Huh7 cells. Blockade of NKG2D, TRAIL, and FASL significantly reduced the cytotoxicity of HI NK cells against SNU398 cells, but blockade of PD-L1 did not lead to any significant change. However, HI NK cells produced IFN-γ well in response to Huh7 cells. In conclusion, the cytotoxicity of HI CD56bright NK cells was attributed to the expression of NKG2D, TRAIL, and FASL. The results suggest the possible use of HI NK cells for cancer immunotherapy and prescreening of HCC cells to help identify the most effective NK cell therapy recipients. View Full-Text
Keywords: hepatic intrasinusoidal NK cells; liver-associated NK cells; hepatocellular carcinoma; cytotoxicity; CD56bright NK cells; NKG2D; TRAIL; FASL; cancer immunotherapy hepatic intrasinusoidal NK cells; liver-associated NK cells; hepatocellular carcinoma; cytotoxicity; CD56bright NK cells; NKG2D; TRAIL; FASL; cancer immunotherapy
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MDPI and ACS Style

Hwang, S.; Han, J.; Baek, J.-S.; Tak, E.; Song, G.-W.; Lee, S.-G.; Jung, D.-H.; Park, G.-C.; Ahn, C.-S.; Kim, N. Cytotoxicity of Human Hepatic Intrasinusoidal CD56bright Natural Killer Cells against Hepatocellular Carcinoma Cells. Int. J. Mol. Sci. 2019, 20, 1564. https://doi.org/10.3390/ijms20071564

AMA Style

Hwang S, Han J, Baek J-S, Tak E, Song G-W, Lee S-G, Jung D-H, Park G-C, Ahn C-S, Kim N. Cytotoxicity of Human Hepatic Intrasinusoidal CD56bright Natural Killer Cells against Hepatocellular Carcinoma Cells. International Journal of Molecular Sciences. 2019; 20(7):1564. https://doi.org/10.3390/ijms20071564

Chicago/Turabian Style

Hwang, Shin; Han, Jaeseok; Baek, Ji-Seok; Tak, Eunyoung; Song, Gi-Won; Lee, Sung-Gyu; Jung, Dong-Hwan; Park, Gil-Chun; Ahn, Chul-Soo; Kim, Nayoung. 2019. "Cytotoxicity of Human Hepatic Intrasinusoidal CD56bright Natural Killer Cells against Hepatocellular Carcinoma Cells" Int. J. Mol. Sci. 20, no. 7: 1564. https://doi.org/10.3390/ijms20071564

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