Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/21708
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dc.contributor.authorJacquelot, Nicolas-
dc.contributor.authorYamazaki, Takahiro-
dc.contributor.authorRoberti, Maria P-
dc.contributor.authorDuong, Connie P M-
dc.contributor.authorAndrews, Miles C-
dc.contributor.authorVerlingue, Loic-
dc.contributor.authorFerrere, Gladys-
dc.contributor.authorBecharef, Sonia-
dc.contributor.authorVétizou, Marie-
dc.contributor.authorDaillère, Romain-
dc.contributor.authorMessaoudene, Meriem-
dc.contributor.authorEnot, David P-
dc.contributor.authorStoll, Gautier-
dc.contributor.authorUgel, Stefano-
dc.contributor.authorMarigo, Ilaria-
dc.contributor.authorFoong Ngiow, Shin-
dc.contributor.authorMarabelle, Aurélien-
dc.contributor.authorPrevost-Blondel, Armelle-
dc.contributor.authorGaudreau, Pierre-Olivier-
dc.contributor.authorGopalakrishnan, Vancheswaran-
dc.contributor.authorEggermont, Alexander M-
dc.contributor.authorOpolon, Paule-
dc.contributor.authorKlein, Christophe-
dc.contributor.authorMadonna, Gabriele-
dc.contributor.authorAscierto, Paolo A-
dc.contributor.authorSucker, Antje-
dc.contributor.authorSchadendorf, Dirk-
dc.contributor.authorSmyth, Mark J-
dc.contributor.authorSoria, Jean-Charles-
dc.contributor.authorKroemer, Guido-
dc.contributor.authorBronte, Vincenzo-
dc.contributor.authorWargo, Jennifer-
dc.contributor.authorZitvogel, Laurence-
dc.date2019-09-03-
dc.date.accessioned2019-09-09T00:42:28Z-
dc.date.available2019-09-09T00:42:28Z-
dc.date.issued2019-10-
dc.identifier.citationCell research 2019; 29(10): 846-861en
dc.identifier.urihttps://ahro.austin.org.au/austinjspui/handle/1/21708-
dc.description.abstractPD-1 blockade represents a major therapeutic avenue in anticancer immunotherapy. Delineating mechanisms of secondary resistance to this strategy is increasingly important. Here, we identified the deleterious role of signaling via the type I interferon (IFN) receptor in tumor and antigen presenting cells, that induced the expression of nitric oxide synthase 2 (NOS2), associated with intratumor accumulation of regulatory T cells (Treg) and myeloid cells and acquired resistance to anti-PD-1 monoclonal antibody (mAb). Sustained IFNβ transcription was observed in resistant tumors, in turn inducing PD-L1 and NOS2 expression in both tumor and dendritic cells (DC). Whereas PD-L1 was not involved in secondary resistance to anti-PD-1 mAb, pharmacological or genetic inhibition of NOS2 maintained long-term control of tumors by PD-1 blockade, through reduction of Treg and DC activation. Resistance to immunotherapies, including anti-PD-1 mAb in melanoma patients, was also correlated with the induction of a type I IFN signature. Hence, the role of type I IFN in response to PD-1 blockade should be revisited as sustained type I IFN signaling may contribute to resistance to therapy.en
dc.language.isoeng-
dc.titleSustained Type I interferon signaling as a mechanism of resistance to PD-1 blockade.en
dc.typeJournal Articleen
dc.identifier.journaltitleCell researchen
dc.identifier.affiliationDepartment of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USAen
dc.identifier.affiliationFaculté de Médecine-Université Paris-Sud, Le Kremlin-Bicêtre, Franceen
dc.identifier.affiliationCIC Biotherapie IGR Curie, CIC1428, Gustave Roussy Cancer Campus, Villejuif, Franceen
dc.identifier.affiliationDepartment of Surgical Oncology, MD Anderson Cancer Center, Houston, TX, USAen
dc.identifier.affiliationMetabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, Franceen
dc.identifier.affiliationINSERM U1138, Centre de Recherche des Cordeliers, Paris, Franceen
dc.identifier.affiliationEquipe 11 labellisée par la Ligue contre le Cancer, Centre de Recherche des Cordeliers, Paris, Franceen
dc.identifier.affiliationUniversité Pierre et Marie Curie, Paris, Franceen
dc.identifier.affiliationUniversité Paris Descartes, Sorbonne Paris Cité, Paris, Franceen
dc.identifier.affiliationPôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, Franceen
dc.identifier.affiliationDepartment of Women's and Children's Health, Karolinska Institute, Karolinska University Hospital, Stockholm, Swedenen
dc.identifier.affiliationDrug Development Department (DITEP), Gustave Roussy, Université Paris-Sud, Université Paris-Saclay, Villejuif, Franceen
dc.identifier.affiliationImmunology in Cancer and Infection Laboratory, QIMR Berghofer Medical Research Institute, Herston, QLD, Australiaen
dc.identifier.affiliationINSERM, U1016, Institut Cochin, Paris, Franceen
dc.identifier.affiliationCNRS, UMR8104, Paris, Franceen
dc.identifier.affiliationInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, Franceen
dc.identifier.affiliationUniversité Paris Descartes, Sorbonne Paris Cité, Paris, Franceen
dc.identifier.affiliationMetabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, Franceen
dc.identifier.affiliationOlivia Newton-John Cancer Research Institute, Heidelberg, Victoria, Australiaen
dc.identifier.affiliationImmunology Division, The Walter and Eliza Hall Institute of Medical Research, Melbourne, VIC, Australiaen
dc.identifier.affiliationSchool of Cancer Medicine, La Trobe University, Heidelberg, VIC, Australiaen
dc.identifier.affiliationSchool of Medicine, University of Queensland, Herston, QLD, Australiaen
dc.identifier.affiliationINSERM U1015, Gustave Roussy, 114 rue Edouard Vaillant, 94805, Villejuif Cedex, Franceen
dc.identifier.affiliationUniversité Paris-Saclay, Le Kremlin-Bicêtre, Franceen
dc.identifier.affiliationInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, Franceen
dc.identifier.affiliationDepartment of Medicine, Verona University Hospital, Verona, Italyen
dc.identifier.affiliationIstituto Oncologico Veneto IOV-IRCCS, Padova, Italyen
dc.identifier.affiliationInstitut de Cancérologie Gustave Roussy Cancer Campus (GRCC), 114 rue Edouard Vaillant, Villejuif, Franceen
dc.identifier.affiliationINSERM U1138, Centre de Recherche des Cordeliers, Paris, Franceen
dc.identifier.affiliationMelanoma Cancer Immunotherapy and Innovative Therapy Unit, Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale", Napoli, Italyen
dc.identifier.affiliationDepartment of Dermatology, University Hospital, University Duisburg-Essen, Essen, Germany & German Cancer Consortium (DKTZ), Heidelberg, Germanyen
dc.identifier.affiliationDepartment of Medicine, Verona University Hospital, Verona, Italyen
dc.identifier.doi10.1038/s41422-019-0224-xen
dc.type.contentTexten
dc.identifier.orcid0000-0001-5788-6840en
dc.identifier.orcid0000-0002-9067-8557en
dc.identifier.orcid0000-0003-1231-8641en
dc.identifier.orcid0000-0002-7268-5905en
dc.identifier.orcid0000-0002-8322-475Xen
dc.identifier.orcid0000-0003-3524-7858en
dc.identifier.orcid0000-0001-7098-7240en
dc.identifier.orcid0000-0002-9334-4405en
dc.identifier.orcid0000-0003-3438-7576en
dc.identifier.pubmedid31481761-
dc.type.austinJournal Article-
item.openairetypeJournal Article-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.grantfulltextnone-
item.fulltextNo Fulltext-
item.cerifentitytypePublications-
item.languageiso639-1en-
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