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

被引：16

作者：

Hwang, Shin ^{[1
]}

Han, Jaeseok ^{[2
,3
]}

Baek, Ji-Seok ^{[2
,3
]}

Tak, Eunyoung ^{[2
,3
]}

Song, Gi-Won ^{[1
]}

Lee, Sung-Gyu ^{[1
]}

Jung, Dong-Hwan ^{[1
]}

Park, Gil-Chun ^{[1
]}

Ahn, Chul-Soo ^{[1
]}

Kim, Nayoung ^{[2
,3
]}

机构：

[1] Univ Ulsan, Coll Med, Dept Surg, Div Liver Transplantat & Hepatobiliary Surg, Seoul 05505, South Korea

[2] Univ Ulsan, Coll Med, Asan Med Ctr, Dept Convergence Med, Seoul 05505, South Korea

[3] Univ Ulsan, Coll Med, Asan Med Ctr, Asan Inst Life Sci, Seoul 05505, South Korea

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2019年 / 20卷 / 07期

基金：

新加坡国家研究基金会;

关键词：

hepatic intrasinusoidal NK cells; liver-associated NK cells; hepatocellular carcinoma; cytotoxicity; CD56(bright) NK cells; NKG2D; TRAIL; FASL; cancer immunotherapy; NK CELLS; UL16-BINDING PROTEIN; RECURRENCE RATES; T-CELLS; LIVER; SUBSET; IDENTIFICATION; IMMUNOTHERAPY; LYMPHOCYTES; ACTIVATION;

D O I：

10.3390/ijms20071564

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 CD56(bright) 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 CD56(bright) NK cells degranulated much less to Huh7 cells. HI CD56(bright) NK cells expressed NKG2D, NKp46, TNF-related apoptosis-inducing ligand (TRAIL), and FAS ligand (FASL) at higher levels than CD56(dim) 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-gamma well in response to Huh7 cells. In conclusion, the cytotoxicity of HI CD56(bright) 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.

引用

页数：15

共 44 条

[1] RAET1E2, a soluble isoform of the UL16-binding protein RAET1E produced by tumor cells, inhibits NKG2D-mediated NK cytotoxicity [J].