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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 5/2017

01-05-2017 | Original Article

Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress

Authors: Kousaku Mimura, Ley-Fang Kua, Noriko Shimasaki, Kensuke Shiraishi, Shotaro Nakajima, Lim Kee Siang, Asim Shabbir, Jimmy So, Wei-Peng Yong, Koji Kono

Published in: Cancer Immunology, Immunotherapy | Issue 5/2017

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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.
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Metadata
Title
Upregulation of thioredoxin-1 in activated human NK cells confers increased tolerance to oxidative stress
Authors
Kousaku Mimura
Ley-Fang Kua
Noriko Shimasaki
Kensuke Shiraishi
Shotaro Nakajima
Lim Kee Siang
Asim Shabbir
Jimmy So
Wei-Peng Yong
Koji Kono
Publication date
01-05-2017
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 5/2017
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-017-1969-z

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