Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells
| Autor(a) principal: | |
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| Data de Publicação: | 2014 |
| Outros Autores: | , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | https://doi.org/10.1016/j.molonc.2014.02.008 |
Resumo: | This 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). |
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Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cellsCD44Dendritic cellsImmunological potencyMucinsSialyl-TnT cellsMolecular MedicineGeneticsCancer ResearchSDG 3 - Good Health and Well-beingThis 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).Despite 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.Centro de Estudos de Doenças Crónicas (CEDOC)NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)RUNCarrascal, Mylene ASeverino, Paulo FCabral, M GuadalupeSilva, MarianaFerreira, José AlexandreCalais, FernandoQuinto, HermíniaPen, CláudiaLigeiro, DárioSantos, Lúcio LaraDall'Olio, FabioVideira, Paula A.2017-09-19T22:03:26Z2014-052014-05-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article13application/pdfhttps://doi.org/10.1016/j.molonc.2014.02.008eng1574-7891PURE: 3140941http://www.scopus.com/inward/record.url?scp=84899482681&partnerID=8YFLogxKhttps://doi.org/10.1016/j.molonc.2014.02.008info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T04:11:42Zoai:run.unl.pt:10362/23448Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:27:47.954060Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| title |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| spellingShingle |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells Carrascal, Mylene A CD44 Dendritic cells Immunological potency Mucins Sialyl-Tn T cells Molecular Medicine Genetics Cancer Research SDG 3 - Good Health and Well-being |
| title_short |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| title_full |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| title_fullStr |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| title_full_unstemmed |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| title_sort |
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells |
| author |
Carrascal, Mylene A |
| author_facet |
Carrascal, Mylene A Severino, Paulo F Cabral, M Guadalupe Silva, Mariana Ferreira, José Alexandre Calais, Fernando Quinto, Hermínia Pen, Cláudia Ligeiro, Dário Santos, Lúcio Lara Dall'Olio, Fabio Videira, Paula A. |
| author_role |
author |
| author2 |
Severino, Paulo F Cabral, M Guadalupe Silva, Mariana Ferreira, José Alexandre Calais, Fernando Quinto, Hermínia Pen, Cláudia Ligeiro, Dário Santos, Lúcio Lara Dall'Olio, Fabio Videira, Paula A. |
| author2_role |
author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Centro de Estudos de Doenças Crónicas (CEDOC) NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM) RUN |
| dc.contributor.author.fl_str_mv |
Carrascal, Mylene A Severino, Paulo F Cabral, M Guadalupe Silva, Mariana Ferreira, José Alexandre Calais, Fernando Quinto, Hermínia Pen, Cláudia Ligeiro, Dário Santos, Lúcio Lara Dall'Olio, Fabio Videira, Paula A. |
| dc.subject.por.fl_str_mv |
CD44 Dendritic cells Immunological potency Mucins Sialyl-Tn T cells Molecular Medicine Genetics Cancer Research SDG 3 - Good Health and Well-being |
| topic |
CD44 Dendritic cells Immunological potency Mucins Sialyl-Tn T cells Molecular Medicine Genetics Cancer Research SDG 3 - Good Health and Well-being |
| description |
This 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). |
| publishDate |
2014 |
| dc.date.none.fl_str_mv |
2014-05 2014-05-01T00:00:00Z 2017-09-19T22:03:26Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
https://doi.org/10.1016/j.molonc.2014.02.008 |
| url |
https://doi.org/10.1016/j.molonc.2014.02.008 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1574-7891 PURE: 3140941 http://www.scopus.com/inward/record.url?scp=84899482681&partnerID=8YFLogxK https://doi.org/10.1016/j.molonc.2014.02.008 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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13 application/pdf |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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