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dc.contributor.authorGras Navarro, Andreaen_US
dc.contributor.authorKmiecik, Justynaen_US
dc.contributor.authorLeiss, Lina Wiken_US
dc.contributor.authorZelkowski, Mateuszen_US
dc.contributor.authorEngelsen, Agneteen_US
dc.contributor.authorBruserud, Øysteinen_US
dc.contributor.authorZimmer, Jacquesen_US
dc.contributor.authorEnger, Per Øyvinden_US
dc.contributor.authorChekenya, Marthaen_US
dc.date.accessioned2017-09-22T11:27:56Z
dc.date.available2017-09-22T11:27:56Z
dc.date.issued2014-12
dc.PublishedGras Navarro A, Kmiecik J, Leiss LW, Zelkowski, Engelsen A, Bruserud Ø, Zimmer J, Enger PØ, Chekenya M. NK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survival. Journal of Immunology. 2014;193(12):6192-6206eng
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.urihttps://hdl.handle.net/1956/16716
dc.description.abstractGlioblastomas (GBMs) are lethal brain cancers that are resistant to current therapies. We investigated the cytotoxicity of human allogeneic NK cells against patient-derived GBM in vitro and in vivo, as well as mechanisms mediating their efficacy. We demonstrate that KIR2DS2 immunogenotype NK cells were more potent killers, notwithstanding the absence of inhibitory killer Ig–like receptor (KIR)-HLA ligand mismatch. FACS-sorted and enriched KIR2DS2+ NK cell subpopulations retained significantly high levels of CD69 and CD16 when in contact with GBM cells at a 1:1 ratio and highly expressed CD107a and secreted more soluble CD137 and granzyme A. In contrast, KIR2DS2− immunogenotype donor NK cells were less cytotoxic against GBM and K562, and, similar to FACS-sorted or gated KIR2DS2− NK cells, significantly diminished CD16, CD107a, granzyme A, and CD69 when in contact with GBM cells. Furthermore, NK cell–mediated GBM killing in vitro depended upon the expression of ligands for the activating receptor NKG2D and was partially abrogated by Ab blockade. Treatment of GBM xenografts in NOD/SCID mice with NK cells from a KIR2DS2+ donor lacking inhibitory KIR-HLA ligand mismatch significantly prolonged the median survival to 163 d compared with vehicle controls (log-rank test, p = 0.0001), in contrast to 117.5 d (log-rank test, p = 0.0005) for NK cells with several inhibitory KIR-HLA ligand mismatches but lacking KIR2DS2 genotype. Significantly more CD56+CD16+ NK cells from a KIR2DS2+ donor survived in nontumor-bearing brains 3 wk after infusion compared with KIR2DS2− NK cells, independent of their proliferative capacity. In conclusion, KIR2DS2 identifies potent alloreactive NK cells against GBM that are mediated by commensurate, but dominant, activating signals.en_US
dc.language.isoengeng
dc.publisherAmerican Association of Immunologistseng
dc.titleNK cells with KIR2DS2 immunogenotype have a functional activation advantage to efficiently kill glioblastoma and prolong animal survivalen_US
dc.typePeer reviewed
dc.typeJournal article
dc.date.updated2017-08-24T08:34:03Z
dc.description.versionpublishedVersionen_US
dc.rights.holderCopyright 2014 by The American Association of Immunologists, Inc.
dc.identifier.doihttps://doi.org/10.4049/jimmunol.1400859
dc.identifier.cristin1215367
dc.source.journalJournal of Immunology
dc.subject.nsiVDP::Medisinske fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710::Medisinsk immunologi: 716
dc.subject.nsiVDP::Midical sciences: 700::Basic medical, dental and veterinary sciences: 710::Medical immunology: 716


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