Please use this identifier to cite or link to this item: https://doi.org/10.1007/s00262-017-1969-z
Title: Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress
Authors: Mimura K.
Kua L.-F.
Shimasaki N.
Shiraishi K.
Nakajima S.
Siang L.K.
Shabbir A. 
So J. 
Yong W.-P.
Kono K.
Keywords: Hydrogen Peroxide
IL-2
Immune surveillance
NK cells
Thioredoxin-1
Issue Date: 1-May-2017
Publisher: Springer Science and Business Media Deutschland GmbH
Citation: Mimura K., Kua L.-F., Shimasaki N., Shiraishi K., Nakajima S., Siang L.K., Shabbir A., So J., Yong W.-P., Kono K. (2017-05-01). Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress. Cancer Immunology, Immunotherapy 66 (5) : 605-613. ScholarBank@NUS Repository. https://doi.org/10.1007/s00262-017-1969-z
Abstract: Adoptive transfer of immune cells, such as T lymphocytes and NK cells, has potential to control cancer growth. However, this can be counteracted by immune escape mechanisms within the tumor microenvironment, including those mediated by reactive oxygen species (ROS). Here, we determined the levels of anti-oxidant molecules in NK cells and their capacity to overcome ROS-induced immune suppression. We investigated the effect of H2O2 on resting NK cells, IL-2-activated NK cells and NK cells expanded by coculture with the K562 leukemia cell line genetically modified to express membrane-bound IL-15 and 4-1BB ligand (K562-mb15-41BBL). Expression of anti-oxidant and anti-apoptotic genes was evaluated by expression array, and protein levels of anti-oxidant molecules by Western blot. Activated NK cells, IL-2-activated NK cells and NK cells expanded by K562-mb15-41BBL were significantly more resistant to H2O2-induced cell death than resting NK. Thioredoxin-1 (TXN1) and peroxiredoxin-1 (PRDX1) were also up-regulated in activated NK cells. Moreover, H2O2-induced cell death after IL-2 activation was significantly induced in the presence of an anti-TXN1-neutralising antibody. Collectively, these data document that activated NK cells can resist to H2O2-induced cell death by up-regulation of TXN1. � 2017, Springer-Verlag Berlin Heidelberg.
Source Title: Cancer Immunology, Immunotherapy
URI: http://scholarbank.nus.edu.sg/handle/10635/146732
ISSN: 03407004
DOI: 10.1007/s00262-017-1969-z
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