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Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade

dc.rights.licenseopenen_US
dc.contributor.authorHOLZGRUBER, Julia
dc.contributor.authorMARTINS, Christina
dc.contributor.authorKULCSAR, Zsofi
dc.contributor.authorDUPLAINE, Alexandra
dc.contributor.authorRASBACH, Erik
dc.contributor.authorMIGAYRON, Laure
dc.contributor.authorSINGH, Praveen
dc.contributor.authorSTATHAM, Edith
dc.contributor.authorLANDSBERG, Jennifer
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorBONIFACE, Katia
hal.structure.identifierImmunology from Concept and Experiments to Translation = Immunologie Conceptuelle, Expérimentale et Translationnelle [ImmunoConcept]
dc.contributor.authorSENESCHAL, Julien
dc.contributor.authorHOETZENECKER, Wolfram
dc.contributor.authorBERDAN, Emma L.
dc.contributor.authorHO SUI, Shannan
dc.contributor.authorRAMSEY, Matthew R.
dc.contributor.authorBARTHEL, Steven R.
dc.contributor.authorSCHATTON, Tobias
dc.date.accessioned2025-01-29T15:22:32Z
dc.date.available2025-01-29T15:22:32Z
dc.date.issued2024-08
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/204635
dc.description.abstractEnProgrammed cell death 1 (PD-1) is a premier cancer drug target for immune checkpoint blockade (ICB). Because PD-1 receptor inhibition activates tumor-specific T-cell immunity, research has predominantly focused on T-cell-PD-1 expression and its immunobiology. In contrast, cancer cell-intrinsic PD-1 functional regulation is not well understood. Here, we demonstrate induction of PD-1 in melanoma cells via type I interferon receptor (IFNAR) signaling and reversal of ICB efficacy through IFNAR pathway inhibition. Treatment of melanoma cells with IFN-α or IFN-β triggers IFNAR-mediated Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling, increases chromatin accessibility and resultant STAT1/2 and IFN regulatory factor 9 (IRF9) binding within a PD-1 gene enhancer, and leads to PD-1 induction. IFNAR1 or JAK/STAT inhibition suppresses melanoma-PD-1 expression and disrupts ICB efficacy in preclinical models. Our results uncover type I IFN-dependent regulation of cancer cell-PD-1 and provide mechanistic insight into the potential unintended ICB-neutralizing effects of widely used IFNAR1 and JAK inhibitors.
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.title.enType I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade
dc.typeArticle de revueen_US
dc.identifier.doi10.1038/s41467-024-51496-2en_US
dc.subject.halSciences du Vivant [q-bio]/Immunologieen_US
dc.identifier.pubmed39187481en_US
bordeaux.journalNature Communicationsen_US
bordeaux.volume15en_US
bordeaux.hal.laboratoriesImmunoConcEpT - UMR 5164en_US
bordeaux.issue1en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
hal.identifierhal-04919563
hal.version1
hal.date.transferred2025-01-29T15:22:37Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccCC BY-NC-NDen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Nature%20Communications&rft.date=2024-08&rft.volume=15&rft.issue=1&rft.au=HOLZGRUBER,%20Julia&MARTINS,%20Christina&KULCSAR,%20Zsofi&DUPLAINE,%20Alexandra&RASBACH,%20Erik&rft.genre=article


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