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

2013Journal article Open access
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dc.contributor.authorLima, Luís
dc.contributor.authorSeverino, Paulo
dc.contributor.authorSilva, Mariana
dc.contributor.authorMiranda, Andreia
dc.contributor.authorTavares, Ana
dc.contributor.authorPereira, Sofia
dc.contributor.authorFernandes, Elisabete
dc.contributor.authorCruz, Ricardo
dc.contributor.authorAmaro, Teresina
dc.contributor.authorReis, Celso
dc.contributor.authorDall'Olio, Fabio
dc.contributor.authorAmado, Francisco
dc.contributor.authorVideira, Paula
dc.contributor.authorSantos, Lúcio
dc.contributor.authorFerreira, José Alexandre
dc.date.accessioned2013-12-31T16:37:44Z
dc.date.available2013-12-31T16:37:44Z
dc.date.issued2013
dc.description.abstractHigh 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 multifocality (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.por
dc.identifier.doi10.1038/bjc.2013.571pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.22/3171
dc.language.isoeng
dc.peerreviewedyespor
dc.publisherCancer Research UK
dc.relation.ispartofseriesBritish Journal of Cancer; Vol. 109
dc.relation.publisherversionhttp://www.nature.com/bjc/journal/v109/n8/full/bjc2013571a.html
dc.subjectBacillus Calmette-Guerinpor
dc.subjectBCG immunotherapypor
dc.subjectBladder Cancerpor
dc.subjectSialyl-Tnpor
dc.subjectSialyl-6-Tpor
dc.subjectTumor glycosylationpor
dc.titleResponse of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapypor
dc.typejournal article
dspace.entity.typePublication
oaire.citation.endPage2114por
oaire.citation.startPage2106por
oaire.citation.titleBritish Journal of Cancerpor
oaire.citation.volumeVol. 109por
person.familyNameOliveira Lima
person.givenNameLuís Carlos
person.identifier.ciencia-id9F16-0E29-D9FC
person.identifier.orcid0000-0001-8152-9237
person.identifier.scopus-author-id23501978900
rcaap.rightsopenAccesspor
rcaap.typearticlepor
relation.isAuthorOfPublicationc6b00c1f-f4c9-4f4f-b291-17cf30b1e1f8
relation.isAuthorOfPublication.latestForDiscoveryc6b00c1f-f4c9-4f4f-b291-17cf30b1e1f8

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