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dc.contributor.authorHühn, Daniela
dc.contributor.authorMartí-Rodrigo, Pablo
dc.contributor.authorMouron, Silvana
dc.contributor.authorHansel, Catherine
dc.contributor.authorTschapalda, Kirsten
dc.contributor.authorPorebski, Bartlomiej
dc.contributor.authorHäggblad, Maria
dc.contributor.authorLidemalm, Louise
dc.contributor.authorCarreras-Puigvert, Jordi
dc.contributor.authorQuintela Fandino, Miguel Angel 
dc.contributor.authorFernandez-Capetillo, Oscar 
dc.date.accessioned2022-03-03T10:45:44Z
dc.date.available2022-03-03T10:45:44Z
dc.date.issued2022-01-16
dc.identifier.citationMol Oncol . 2022 Jan;16(1):148-165.es_ES
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13714
dc.description.abstractAmong others, expression levels of programmed cell death 1 ligand 1 (PD-L1) have been explored as biomarkers of the response to immune checkpoint inhibitors in cancer therapy. Here, we present the results of a chemical screen that interrogated how medically approved drugs influence PD-L1 expression. As expected, corticosteroids and inhibitors of Janus kinases were among the top PD-L1 downregulators. In addition, we identified that PD-L1 expression is induced by antiestrogenic compounds. Transcriptomic analyses indicate that chronic estrogen receptor alpha (ERα) inhibition triggers a broad immunosuppressive program in ER-positive breast cancer cells, which is subsequent to their growth arrest and involves the activation of multiple immune checkpoints together with the silencing of the antigen-presenting machinery. Accordingly, estrogen-deprived MCF7 cells are resistant to T-cell-mediated cell killing, in a manner that is independent of PD-L1, but which is reverted by estradiol. Our study reveals that while antiestrogen therapies efficiently limit the growth of ER-positive breast cancer cells, they concomitantly trigger a transcriptional program that favors their immune evasion.es_ES
dc.description.sponsorshipWe would want to thank Andres J Lopez-Contreras for insightful comments on the manuscript, Hana Imrichova for help with GSEAs, and the core facility at NEO, BEA, Bioinformatics and Expression Analysis, which is supported by the board of research at the Karolinska Institute and the research committee at the Karolinska Hospital. Research was funded by grants from the Cancerfonden Foundation (CAN 2018/381) and the Swedish Research Council (VR) (538-2014-31) to OF and from the ISCIII (AES-PI16/00354; cofunded by the European Regional Development Fund) and from the Call for Coordinated Research Groups from Madrid Region, Madrid Regional Government-ERDF Funds (B2017/BMD3733) to MQ-F. This research was supported by Consejería de Sanidad, Comunidad de Madrid.es_ES
dc.language.isoenges_ES
dc.publisherWiley es_ES
dc.type.hasVersionVoRes_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectBREAST-CANCER PATIENTSes_ES
dc.subjectEstrogen receptores_ES
dc.subjectHLAes_ES
dc.subjectIMMUNOTHERAPYes_ES
dc.subjectINFLAMMATIONes_ES
dc.subjectPD-L1es_ES
dc.titleProlonged estrogen deprivation triggers a broad immunosuppressive phenotype in breast cancer cells.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.pubmedID34392603es_ES
dc.format.volume16es_ES
dc.format.number1es_ES
dc.format.page148-165es_ES
dc.identifier.doi10.1002/1878-0261.13083es_ES
dc.contributor.funderKarolinska Institutet es_ES
dc.contributor.funderCancerfonden Foundationes_ES
dc.contributor.funderSwedish Research Council es_ES
dc.contributor.funderInstituto de Salud Carlos III es_ES
dc.contributor.funderUnión Europea. Comisión Europea es_ES
dc.contributor.funderComunidad de Madrid (España) es_ES
dc.description.peerreviewedes_ES
dc.identifier.e-issn1878-0261es_ES
dc.relation.publisherversionhttps://doi.org/10.1002/1878-0261.13083.es_ES
dc.identifier.journalMolecular oncologyes_ES
dc.repisalud.institucionCNIOes_ES
dc.repisalud.orgCNIOCNIO::Grupos de investigación::Grupo de Inestabilidad Genómicaes_ES
dc.rights.accessRightsopen accesses_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/AES-PI16/00354es_ES
dc.relation.projectFISinfo:eu-repo/grantAgreement/B2017/BMD3733es_ES


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