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Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells

2014-05Artigo científico Acesso aberto
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dc.contributor.authorCarrascal, Mylene A
dc.contributor.authorSeverino, Paulo F
dc.contributor.authorCabral, M Guadalupe
dc.contributor.authorCabral, MG
dc.contributor.authorSilva, Mariana
dc.contributor.authorFerreira, José Alexandre
dc.contributor.authorCalais, Fernando
dc.contributor.authorQuinto, Hermínia
dc.contributor.authorPen, Cláudia
dc.contributor.authorLigeiro, Dário
dc.contributor.authorSantos, Lúcio Lara
dc.contributor.authorDall'Olio, Fabio
dc.contributor.authorVideira, Paula A.
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.pblWiley
dc.date.accessioned2017-09-19T22:03:26Z
dc.date.available2017-09-19T22:03:26Z
dc.date.issued2014-05
dc.descriptionThis work was supported by the Portuguese Foundation for Science and Technology (FCT) - PTDC/SAU-MII/67561/2006 and Premio Santander Totta - UNL (Paula A. Videira), LPCC/Pfizer2011 (Mylene A. Carrascal), SFRH/BPD/21619/2005 (M. Guadalupe Cabral), SFRH/BD/81860/2011 (Mariana Silva), SFRH/BD/45120/2008 (Paulo F. Severino) and SFRH/BPD/ 66288/2009 (Jose Alexandre Ferreira). FCT is co-financed by European Social Fund (ESF) under Human Potential Operation Programme (POPH) from National Strategic Reference Framework (NSRF).) and European Union, QREN, FEDER, COMPETE, for funding the Organic Chemistry Research Unit (QOPNA) (project PEst-C/QUI/UI0062/2013; FCOMP-01-0124-FEDER-037296).
dc.description.abstractDespite the wide acceptance that glycans are centrally implicated in immunity, exactly how they contribute to the tilt immune response remains poorly defined. In this study, we sought to evaluate the impact of the malignant phenotype-associated glycan, sialyl-Tn (STn) in the function of the key orchestrators of the immune response, the dendritic cells (DCs). In high grade bladder cancer tissue, the STn antigen is significantly overexpressed and correlated with the increased expression of ST6GALNAC1 sialyltransferase. Bladder cancer tissue presenting elevated expression of ST6GALNAC1 showed a correlation with increased expression of CD1a, a marker for bladder immature DCs and showed concomitant low levels of Th1-inducing cytokines IL-12 and TNF-α. Invitro, human DCs co-incubated with STn+ bladder cancer cells, had an immature phenotype (MHC-IIlow, CD80low and CD86low) and were unresponsive to further maturation stimuli. When contacting with STn+ cancer cells, DCs expressed significantly less IL-12 and TNF-α. Consistent with a tolerogenic DC profile, T cells that were primed by DCs pulsed with antigens derived from STn+ cancer cells were not activated and showed a FoxP3high IFN-γlow phenotype. Blockade of STn antigens and of STn+ glycoprotein, CD44 and MUC1, in STn+ cancer cells was able to lower the induction of tolerance and DCs become more mature.Overall, our data suggest that STn-expressing cancer cells impair DC maturation and endow DCs with a tolerogenic function, limiting their capacity to trigger protective anti-tumour T cell responses. STn antigens and, in particular, STn+ glycoproteins are potential targets for circumventing tumour-induced tolerogenic mechanisms.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent13
dc.format.extent1563902
dc.identifier.doi10.1016/j.molonc.2014.02.008
dc.identifier.issn1574-7891
dc.identifier.otherPURE: 3140941
dc.identifier.otherPURE UUID: 8dd38440-a2c7-4a94-9a60-6997fec71239
dc.identifier.otherScopus: 84899482681
dc.identifier.otherPubMed: 24656965
dc.identifier.otherWOS: 000336472100026
dc.identifier.otherORCID: /0000-0001-5987-2485/work/43388115
dc.identifier.urihttp://www.scopus.com/inward/record.url?scp=84899482681&partnerID=8YFLogxK
dc.identifier.urlhttps://www.scopus.com/pages/publications/84899482681
dc.language.isoeng
dc.peerreviewedyes
dc.relationinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/67561/PT
dc.relationThe role of sialic acid in the immunobiology of dendritic cells
dc.relationELUCIDATING THE SELECTIN LIGANDS IN DENDRITIC CELLS: A CONTRIBUTION TO THE DEVELOPMENT OF DENDRITIC CELL-BASED VACCINES WITH OSTEOTROPISM FOR TREATMENT OF BONE METASTASIS
dc.relationTHOMSEN-FRIEDENREICH ANTIGENS IN BLADDER CANCER: EVALUATION OF THEIR PROGNOSTIC VALUE
dc.subjectCD44
dc.subjectDendritic cells
dc.subjectImmunological potency
dc.subjectMucins
dc.subjectSialyl-Tn
dc.subjectT cells
dc.subjectMolecular Medicine
dc.subjectGenetics
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleSialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cellsen
dc.typejournal article
degois.publication.firstPage753
degois.publication.issue3
degois.publication.lastPage765
degois.publication.titleMolecular Oncology
degois.publication.volume8
dspace.entity.typePublication
oaire.awardNumberPTDC/SAU-MII/67561/2006
oaire.awardNumberSFRH/BPD/21619/2005
oaire.awardNumberSFRH/BD/81860/2011
oaire.awardNumberSFRH/BD/45120/2008
oaire.awardTitleThe role of sialic acid in the immunobiology of dendritic cells
oaire.awardTitleELUCIDATING THE SELECTIN LIGANDS IN DENDRITIC CELLS: A CONTRIBUTION TO THE DEVELOPMENT OF DENDRITIC CELL-BASED VACCINES WITH OSTEOTROPISM FOR TREATMENT OF BONE METASTASIS
oaire.awardTitleTHOMSEN-FRIEDENREICH ANTIGENS IN BLADDER CANCER: EVALUATION OF THEIR PROGNOSTIC VALUE
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/3599-PPCDT/PTDC%2FSAU-MII%2F67561%2F2006/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/SFRH/SFRH%2FBPD%2F21619%2F2005/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F81860%2F2011/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F45120%2F2008/PT
oaire.fundingStream3599-PPCDT
oaire.fundingStreamSFRH
person.familyNameCabral
person.givenNameMaria de Guadalupe
person.identifier.ciencia-idCB1B-C82A-D84A
person.identifier.orcid0000-0001-9016-9173
person.identifier.ridN-4029-2016
person.identifier.scopus-author-id55412398200
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccess
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