Thioredoxin activity confers resistance against oxidative stress in tumor-infiltrating NK cells.

The Journal of Clinical Investigation
Ying YangAndreas Lundqvist

Abstract

To improve the clinical outcome of adoptive NK cell therapy in patients with solid tumors, NK cells need to persist within the tumor microenvironment (TME) in which the abundance of ROS could dampen antitumor immune responses. In the present study, we demonstrated that IL-15-primed NK cells acquired resistance against oxidative stress through the thioredoxin system activated by mTOR. Mechanistically, the activation of thioredoxin showed dependence on localization of thioredoxin-interacting protein. We show that NK cells residing in the tumor core expressed higher thiol densities that could aid in protecting other lymphocytes against ROS within the TME. Furthermore, the prognostic value of IL15 and the NK cell gene signature in tumors may be influenced by tobacco smoking history in patients with non-small-cell lung cancer (NSCLC). Collectively, the levels of reducing antioxidants in NK cells may not only predict better tumor penetrance but potentially even the immune therapy response.

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Citations

Sep 15, 2020·The Journal of Clinical Investigation·Theresa L Whiteside
Feb 16, 2021·Redox Biology·Kilian B Kennel, Florian R Greten
Feb 13, 2021·Antioxidants·Carmen Griñan-LisonSergio Granados-Principal
Mar 19, 2021·Frontiers in Cell and Developmental Biology·Peijie WuNa Xie

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Datasets Mentioned

BETA
GSE127465

Methods Mentioned

BETA
FACS
environmental stress
surgical resections
flow cytometry
density gradient centrifugation
PMA
Assay
PCR
RNA-Seq

Software Mentioned

CaseViewer
SeqGeq
corrplot
GraphPad Prism
3DHISTECH
custom R scripts
FlowJo
CellProfiler
GSEA
survplot

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