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dc.contributor.authorKoyama, Shoheien_US
dc.contributor.authorAkbay, Esra A.en_US
dc.contributor.authorLi, Yvonne Y.en_US
dc.contributor.authorHerter-Sprie, Grit S.en_US
dc.contributor.authorBuczkowski, Kevin A.en_US
dc.contributor.authorRichards, William G.en_US
dc.contributor.authorGandhi, Leenaen_US
dc.contributor.authorRedig, Amanda J.en_US
dc.contributor.authorRodig, Scott J.en_US
dc.contributor.authorAsahina, Hajimeen_US
dc.contributor.authorJones, Robert E.en_US
dc.contributor.authorKulkarni, Meghana M.en_US
dc.contributor.authorKuraguchi, Marien_US
dc.contributor.authorPalakurthi, Sangeethaen_US
dc.contributor.authorFecci, Peter E.en_US
dc.contributor.authorJohnson, Bruce E.en_US
dc.contributor.authorJanne, Pasi A.en_US
dc.contributor.authorEngelman, Jeffrey A.en_US
dc.contributor.authorGangadharan, Sidharta P.en_US
dc.contributor.authorCosta, Daniel B.en_US
dc.contributor.authorFreeman, Gordon J.en_US
dc.contributor.authorBueno, Raphaelen_US
dc.contributor.authorHodi, F. Stephenen_US
dc.contributor.authorDranoff, Glennen_US
dc.contributor.authorWong, Kwok-Kinen_US
dc.contributor.authorHammerman, Peter S.en_US
dc.date.accessioned2016-04-01T15:47:45Z
dc.date.issued2016en_US
dc.identifier.citationKoyama, S., E. A. Akbay, Y. Y. Li, G. S. Herter-Sprie, K. A. Buczkowski, W. G. Richards, L. Gandhi, et al. 2016. “Adaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpoints.” Nature Communications 7 (1): 10501. doi:10.1038/ncomms10501. http://dx.doi.org/10.1038/ncomms10501.en
dc.identifier.issn2041-1723en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:26318574
dc.description.abstractDespite compelling antitumour activity of antibodies targeting the programmed death 1 (PD-1): programmed death ligand 1 (PD-L1) immune checkpoint in lung cancer, resistance to these therapies has increasingly been observed. In this study, to elucidate mechanisms of adaptive resistance, we analyse the tumour immune microenvironment in the context of anti-PD-1 therapy in two fully immunocompetent mouse models of lung adenocarcinoma. In tumours progressing following response to anti-PD-1 therapy, we observe upregulation of alternative immune checkpoints, notably T-cell immunoglobulin mucin-3 (TIM-3), in PD-1 antibody bound T cells and demonstrate a survival advantage with addition of a TIM-3 blocking antibody following failure of PD-1 blockade. Two patients who developed adaptive resistance to anti-PD-1 treatment also show a similar TIM-3 upregulation in blocking antibody-bound T cells at treatment failure. These data suggest that upregulation of TIM-3 and other immune checkpoints may be targetable biomarkers associated with adaptive resistance to PD-1 blockade.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/ncomms10501en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757784/pdf/en
dash.licenseLAAen_US
dc.titleAdaptive resistance to therapeutic PD-1 blockade is associated with upregulation of alternative immune checkpointsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalNature Communicationsen
dash.depositing.authorAkbay, Esra A.en_US
dc.date.available2016-04-01T15:47:45Z
dc.identifier.doi10.1038/ncomms10501*
dash.authorsorderedfalse
dash.contributor.affiliatedAsahina, Hajime
dash.contributor.affiliatedLi, Yvonne Y.
dash.contributor.affiliatedGangadharan, Sidhu
dash.contributor.affiliatedDranoff, Glenn
dash.contributor.affiliatedHerter-Sprie, Grit S.
dash.contributor.affiliatedCosta, Daniel
dash.contributor.affiliatedAkbay, Esra A.
dash.contributor.affiliatedHammerman, Peter S.
dash.contributor.affiliatedFreeman, Gordon
dash.contributor.affiliatedJohnson, Bruce
dash.contributor.affiliatedWong, Kwok-Kin
dash.contributor.affiliatedEngelman, Jeffrey A
dash.contributor.affiliatedJanne, Pasi


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