Indoleamine-2,3-dioxygenase in thyroid cancer cells suppresses natural killer cell function by inhibiting NKG2D and NKp46 expression via STAT signaling pathways

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Title
Indoleamine-2,3-dioxygenase in thyroid cancer cells suppresses natural killer cell function by inhibiting NKG2D and NKp46 expression via STAT signaling pathways
Author(s)
Arum Park; Yunjeong Yang; Yunhee Lee; Mi Sun Kim; Young-Jun ParkHaiyoung JungTae-Don KimHee Gu Lee; In Pyo Choi; Suk Ran Yoon
Bibliographic Citation
Journal of Clinical Medicine, vol. 8, no. 6, pp. 842-842
Publication Year
2019
Abstract
Natural killer (NK) cells are key players in the immune system. They use receptors on their cell surface to identify target cells. However, to escape being killed by the immune system, cancer cells such as thyroid cancer cells, use various methods to suppress the function of NK cells. Thus, this study aims to elucidate how thyroid cancer cells downregulate NK cell function in a co-culture system. We found that thyroid cancer cells suppress NK cell cytotoxicity and inhibit the expression of activating receptors, such as NKG2D and NKp46, by regulating indoleamine 2,3-dioxygenase (IDO). Also, thyroid cancer cells produce kynurenine using IDO, which causes NK cell dysfunction. Kynurenine enters NK cells via the aryl hydrocarbon receptor (AhR) on the surfaces of the NK cells, which decreases NK cell function and NK receptor expression via the signal transducer and activator of transcription (STAT) 1 and STAT3 pathways. In addition, STAT1 and STAT3 directly regulated the expression of NKG2D and NKp46 receptors by binding to the promoter region. Conclusively, NK cell function may be impaired in thyroid cancer patients by IDO-induced kynurenine production. This implies that IDO can be used as a target for thyroid cancer therapeutics aiming at improving NK cell function.
Keyword
NK cellsthyroid cancer cellsindoleamine 2,3-dioxygenasekynurenineNKG2DNKp46STAT1STAT 3
ISSN
2077-0383
Publisher
MDPI
DOI
http://dx.doi.org/10.3390/jcm8060842
Type
Article
Appears in Collections:
Division of Research on National Challenges > Environmental diseases research center > 1. Journal Articles
Aging Convergence Research Center > 1. Journal Articles
Division of Biomedical Research > Immunotherapy Research Center > 1. Journal Articles
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