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Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation

2015-04-29Artigo científico Acesso aberto
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dc.contributor.authorPapaspyridonos, Marianna
dc.contributor.authorMatei, Irina
dc.contributor.authorHuang, Yujie
dc.contributor.authorAndre, Maria do Rosario
dc.contributor.authorBrazier-Mitouart, Helene
dc.contributor.authorWaite, Janelle C.
dc.contributor.authorChan, April S.
dc.contributor.authorKalter, Julie
dc.contributor.authorRamos, Ilyssa
dc.contributor.authorWu, Qi
dc.contributor.authorWilliams, Caitlin
dc.contributor.authorWolchok, Jedd D.
dc.contributor.authorChapman, Paul B.
dc.contributor.authorPeinado, Hector
dc.contributor.authorAnandasabapathy, Niroshana
dc.contributor.authorOcean, Allyson J.
dc.contributor.authorKaplan, Rosandra N.
dc.contributor.authorGreenfield, Jeffrey P.
dc.contributor.authorBromberg, Jacqueline
dc.contributor.authorSkokos, Dimitris
dc.contributor.authorLyden, David
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentre for Toxicogenomics and Human Health (ToxOmics)
dc.contributor.pblNature Portfolio
dc.date.accessioned2017-09-14T22:03:11Z
dc.date.available2017-09-14T22:03:11Z
dc.date.issued2015-04-29
dc.description.abstractA central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent13
dc.format.extent2347907
dc.identifier.doi10.1038/ncomms7840
dc.identifier.issn2041-1723
dc.identifier.otherPURE: 3129873
dc.identifier.otherPURE UUID: 64d8d884-d602-4e69-bf2b-4cb536a457c3
dc.identifier.otherScopus: 84928884360
dc.identifier.otherPubMed: 25924227
dc.identifier.otherWOS: 000353703400007
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=84928884360&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/84928884360
dc.language.isoeng
dc.peerreviewedyes
dc.subjectSELF-RENEWAL CAPACITY
dc.subjectREGULATORY T-CELLS
dc.subjectTGF-BETA
dc.subjectDENDRITIC CELLS
dc.subjectPERIPHERAL-BLOOD
dc.subjectPROGENITOR CELLS
dc.subjectCANCER-PATIENTS
dc.subjectDIFFERENTIATION
dc.subjectPROTEINS
dc.subjectMELANOMA
dc.subjectGeneral Chemistry
dc.subjectGeneral Biochemistry,Genetics and Molecular Biology
dc.subjectGeneral Physics and Astronomy
dc.subjectSDG 3 - Good Health and Well-being
dc.titleId1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturationen
dc.typejournal article
degois.publication.firstPage
degois.publication.lastPage
degois.publication.titleNature Communications
degois.publication.volume6
dspace.entity.typePublication
rcaap.rightsopenAccess

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