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Altered NKp30, NKp46, NKG2D, and DNAM-1 Expression on Circulating NK Cells Is Associated with Tumor Progression in Human Gastric Cancer

Authors :
Bin Han
Fang-yuan Mao
Yong-liang Zhao
Yi-pin Lv
Yong-sheng Teng
Mubing Duan
Weisan Chen
Ping Cheng
Ting-ting Wang
Zhong-yuan Liang
Jin-yu Zhang
Yu-gang Liu
Gang Guo
Quan-ming Zou
Yuan Zhuang
Liu-sheng Peng
Source :
Journal of Immunology Research, Vol 2018 (2018)
Publication Year :
2018
Publisher :
Wiley, 2018.

Abstract

Natural killer (NK) cell activity is influenced by a complex integration of signaling pathways activated downstream of both activating and inhibitory surface receptors. The tumor microenvironment can suppress NK cell activity, and there is a great clinical interest in understanding whether modulating tumor-mediated NK cell suppression and/or boosting preexisting NK cell numbers in cancer patients is therapeutically viable. To this light, we characterized the surface receptor phenotypes of peripheral blood NK cells and examined their clinical relevance to human gastric cancer (GC). We found that the proportion of peripheral blood NK cells which expressed the activating receptors NKp30, NKp46, NKG2D, and DNAM-1 was significantly decreased in GC patients compared to healthy donors, and that this decrease was positively associated with tumor progression. At the same time, plasma TGF-β1 concentrations were significantly increased in GC patients and negatively correlated with the proportion of NKp30, NKp46, NKG2D, and DNAM-1 expressing NK cells. Furthermore, TGF-β1 significantly downregulated the expression of NKp30, NKp46, NKG2D, and DNAM-1 on NK cells in vitro, and the addition of galunisertib, an inhibitor of the TGF-β receptor subunit I, reversed this downregulation. Altogether, our data suggest that the decreased expression of activating receptors NKp30, NKp46, NKG2D, and DNAM-1 on peripheral blood NK cells is positively associated with GC progression, and that TGF-β1-mediated NK cell suppression may be a therapeutically targetable characteristic of GC.

Details

Language :
English
ISSN :
23148861 and 23147156
Volume :
2018
Database :
Directory of Open Access Journals
Journal :
Journal of Immunology Research
Publication Type :
Academic Journal
Accession number :
edsdoj.b34ac744ccf8477da76410edb5c91e13
Document Type :
article
Full Text :
https://doi.org/10.1155/2018/6248590