Artykuł w czasopiśmie
Brak miniatury
Licencja
CC-BY-NC-NDCC-BY-NC-ND - Uznanie autorstwa - Użycie niekomercyjne - Bez utworów zależnych
 

PRDX-1 supports the survival and antitumor activity of primary and CAR-modified NK cells under oxidative stress

Uproszczony widok
cris.lastimport.scopus2024-02-12T20:47:41Z
dc.abstract.enOxidative stress, caused by the imbalance between reactive species generation and the dysfunctional capacity of antioxidant defenses, is one of the characteristic features of cancer. Here, we quantified hydrogen peroxide in the tumor microenvironment (TME) and demonstrated that hydrogen peroxide concentrations are elevated in tumor interstitial fluid isolated from murine breast cancers in vivo, when compared with blood or normal subcutaneous fluid. Therefore, we investigated the effects of increased hydrogen peroxide concentration on immune cell functions. NK cells were more susceptible to hydrogen peroxide than T cells or B cells, and by comparing T, B, and NK cells' sensitivities to redox stress and their antioxidant capacities, we identified peroxiredoxin-1 (PRDX1) as a lacking element of NK cells' antioxidative defense. We observed that priming with IL15 protected NK cells' functions in the presence of high hydrogen peroxide and simultaneously upregulated PRDX1 expression. However, the effect of IL15 on PRDX1 expression was transient and strictly dependent on the presence of the cytokine. Therefore, we genetically modified NK cells to stably overexpress PRDX1, which led to increased survival and NK cell activity in redox stress conditions. Finally, we generated PD-L1-CAR NK cells overexpressing PRDX1 that displayed potent antitumor activity against breast cancer cells under oxidative stress. These results demonstrate that hydrogen peroxide, at concentrations detected in the TME, suppresses NK cell function and that genetic modification strategies can improve CAR NK cells' resistance and potency against solid tumors.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorPlewczyński, Dariusz
dc.contributor.authorKłopotowska, Marta
dc.contributor.authorWiniarska, Magdalena
dc.contributor.authorZagozdzon, Radoslaw
dc.contributor.authorMalmberg, Karl-Johan
dc.contributor.authorNetskar, Herman
dc.contributor.authorLachota, Mieszko
dc.contributor.authorSharma, Blanka
dc.contributor.authorTemples, Madison N
dc.contributor.authorKrawczyk, Marta
dc.contributor.authorRamji, Kavita
dc.contributor.authorRetecki, Kuba
dc.contributor.authorSlusarczyk, Aleksander
dc.contributor.authorMARHELAVA, KATSIARYNA
dc.contributor.authorDomagała, Joanna
dc.contributor.authorSoroczynska, Karolina
dc.contributor.authorGoral, Agnieszka
dc.contributor.authorLazniewski, Michal
dc.contributor.authorBaranowska, Iwona
dc.contributor.authorFirczuk, Malgorzata
dc.contributor.authorZhylko, Andriy
dc.contributor.authorPilch, Zofia
dc.contributor.authorKraft, Agnieszka
dc.contributor.authorGraczyk-Jarzynka, Agnieszka
dc.contributor.authorBajor, Małgorzata
dc.date.accessioned2024-01-25T17:18:39Z
dc.date.available2024-01-25T17:18:39Z
dc.date.copyright2021-12-01
dc.date.issued2022
dc.description.accesstimeBEFORE_PUBLICATION
dc.description.financePublikacja bezkosztowa
dc.description.number2
dc.description.sdgGoodHealthAndWellBeing
dc.description.versionFINAL_PUBLISHED
dc.description.volume10
dc.identifier.doi10.1158/2326-6066.CIR-20-1023
dc.identifier.issn2326-6066
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/116868
dc.identifier.weblinkhttp://cancerimmunolres.aacrjournals.org/
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofCancer immunology research
dc.relation.pages228-244
dc.rightsCC-BY-NC-ND
dc.sciencecloudnosend
dc.subject.enDIFFERENTIAL EXPRESSION ANALYSIS
dc.subject.enTRANSFER
dc.subject.enSUBSET
dc.subject.enROS
dc.subject.enRESISTANT
dc.subject.enEXPANSION
dc.subject.enREACTIVE OXYGEN
dc.subject.enT-CELLS
dc.subject.enHYDROGEN-PEROXIDE
dc.subject.enGENE-EXPRESSION
dc.subject.enADOPTIVE
dc.titlePRDX-1 supports the survival and antitumor activity of primary and CAR-modified NK cells under oxidative stress
dc.typeJournalArticle
dspace.entity.typePublication