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Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy

2013-10-15Artigo científico Acesso aberto
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dc.contributor.authorLima, L.
dc.contributor.authorSeverino, P. F.
dc.contributor.authorSilva, M.
dc.contributor.authorMiranda, A.
dc.contributor.authorTavares, A.
dc.contributor.authorPereira, S.
dc.contributor.authorFernandes, E.
dc.contributor.authorCruz, R.
dc.contributor.authorAmaro, T.
dc.contributor.authorReis, C. A.
dc.contributor.authorDall'Olio, F.
dc.contributor.authorAmado, F.
dc.contributor.authorVideira, P. A.
dc.contributor.authorSantos, L.
dc.contributor.authorFerreira, J. A.
dc.contributor.institutionNOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
dc.contributor.institutionCentro de Estudos de Doenças Crónicas (CEDOC)
dc.contributor.pblNature Publishing Group
dc.date.accessioned2024-02-21T22:19:45Z
dc.date.available2024-02-21T22:19:45Z
dc.date.issued2013-10-15
dc.description.abstractBackground:High risk of recurrence/progression bladder tumours is treated with Bacillus Calmette-Guérin (BCG) immunotherapy after complete resection of the tumour. Approximately 75% of these tumours express the uncommon carbohydrate antigen sialyl-Tn (Tn), a surrogate biomarker of tumour aggressiveness. Such changes in the glycosylation of cell-surface proteins influence tumour microenvironment and immune responses that may modulate treatment outcome and the course of disease. The aim of this work is to determine the efficiency of BCG immunotherapy against tumours expressing sTn and sTn-related antigen sialyl-6-T (s6T).Methods:In a retrospective design, 94 tumours from patients treated with BCG were screened for sTn and s6T expression. In vitro studies were conducted to determine the interaction of BCG with high-grade bladder cancer cell line overexpressing sTn.Results:From the 94 cases evaluated, 36 had recurrence after BCG treatment (38.3%). Treatment outcome was influenced by age over 65 years (HR=2.668; (1.344-5.254); P=0.005), maintenance schedule (HR=0.480; (0.246-0.936); P=0.031) and multifocallity (HR=2.065; (1.033-4.126); P=0.040). sTn or s6T expression was associated with BCG response (P=0.024; P<0.0001) and with increased recurrence-free survival (P=0.001). Multivariate analyses showed that sTn and/or s6T were independent predictive markers of recurrence after BCG immunotherapy (HR=0.296; (0.148-0.594); P=0.001). In vitro studies demonstrated higher adhesion and internalisation of the bacillus to cells expressing sTn, promoting cell death.Conclusion:s6T is described for the first time in bladder tumours. Our data strongly suggest that BCG immunotherapy is efficient against sTn- and s6T-positive tumours. Furthermore, sTn and s6T expression are independent predictive markers of BCG treatment response and may be useful in the identification of patients who could benefit more from this immunotherapy.en
dc.description.versionpublishersversion
dc.description.versionpublished
dc.format.extent9
dc.format.extent1392051
dc.identifier.doi10.1038/bjc.2013.571
dc.identifier.issn0007-0920
dc.identifier.otherPURE: 5305964
dc.identifier.otherPURE UUID: 9fb547e4-4f9a-4089-818e-cdec2b2e5772
dc.identifier.otherScopus: 84885909350
dc.identifier.otherPubMed: 24064971
dc.identifier.otherWOS: 000325795000011
dc.identifier.otherORCID: /0000-0001-5987-2485/work/46572968
dc.identifier.urihttp://hdl.handle.net/10362/163895
dc.identifier.urlhttps://www.scopus.com/pages/publications/84885909350
dc.language.isoeng
dc.peerreviewedyes
dc.subjectBacillus Calmette-Guérin
dc.subjectBCG immunotherapy
dc.subjectbladder cancer
dc.subjectsialyl-6-T
dc.subjectsialyl-Tn
dc.subjecttumour glycosylation
dc.subjectOncology
dc.subjectCancer Research
dc.subjectSDG 3 - Good Health and Well-being
dc.titleResponse of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapyen
dc.typejournal article
degois.publication.firstPage2106
degois.publication.issue8
degois.publication.lastPage2114
degois.publication.titleBritish Journal of Cancer
degois.publication.volume109
dspace.entity.typePublication
rcaap.rightsopenAccess

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