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

Detalhes bibliográficos
Autor(a) principal: Lima, L.
Data de Publicação: 2013
Outros Autores: Severino, P. F., Silva, M., Miranda, A., Tavares, A., Pereira, S., Fernandes, E., Cruz, R., Amaro, T., Reis, C. A., Dall'Olio, F., Amado, F., Videira, P. A., Santos, L., Ferreira, J. A.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10362/163895
Resumo: Background: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.
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spelling Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapyBacillus Calmette-GuérinBCG immunotherapybladder cancersialyl-6-Tsialyl-Tntumour glycosylationOncologyCancer ResearchSDG 3 - Good Health and Well-beingBackground: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.NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)Centro de Estudos de Doenças Crónicas (CEDOC)RUNLima, L.Severino, P. F.Silva, M.Miranda, A.Tavares, A.Pereira, S.Fernandes, E.Cruz, R.Amaro, T.Reis, C. A.Dall'Olio, F.Amado, F.Videira, P. A.Santos, L.Ferreira, J. A.2024-02-21T22:19:45Z2013-10-152013-10-15T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article9application/pdfhttp://hdl.handle.net/10362/163895eng0007-0920PURE: 5305964https://doi.org/10.1038/bjc.2013.571info: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:RCAAP2024-03-11T05:49:29Zoai:run.unl.pt:10362/163895Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:59:55.050011Repositório 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 Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
title Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
spellingShingle Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
Lima, L.
Bacillus Calmette-Guérin
BCG immunotherapy
bladder cancer
sialyl-6-T
sialyl-Tn
tumour glycosylation
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
title_short Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
title_full Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
title_fullStr Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
title_full_unstemmed Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
title_sort Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy
author Lima, L.
author_facet Lima, L.
Severino, P. F.
Silva, M.
Miranda, A.
Tavares, A.
Pereira, S.
Fernandes, E.
Cruz, R.
Amaro, T.
Reis, C. A.
Dall'Olio, F.
Amado, F.
Videira, P. A.
Santos, L.
Ferreira, J. A.
author_role author
author2 Severino, P. F.
Silva, M.
Miranda, A.
Tavares, A.
Pereira, S.
Fernandes, E.
Cruz, R.
Amaro, T.
Reis, C. A.
Dall'Olio, F.
Amado, F.
Videira, P. A.
Santos, L.
Ferreira, J. A.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)
Centro de Estudos de Doenças Crónicas (CEDOC)
RUN
dc.contributor.author.fl_str_mv Lima, L.
Severino, P. F.
Silva, M.
Miranda, A.
Tavares, A.
Pereira, S.
Fernandes, E.
Cruz, R.
Amaro, T.
Reis, C. A.
Dall'Olio, F.
Amado, F.
Videira, P. A.
Santos, L.
Ferreira, J. A.
dc.subject.por.fl_str_mv Bacillus Calmette-Guérin
BCG immunotherapy
bladder cancer
sialyl-6-T
sialyl-Tn
tumour glycosylation
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
topic Bacillus Calmette-Guérin
BCG immunotherapy
bladder cancer
sialyl-6-T
sialyl-Tn
tumour glycosylation
Oncology
Cancer Research
SDG 3 - Good Health and Well-being
description Background: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.
publishDate 2013
dc.date.none.fl_str_mv 2013-10-15
2013-10-15T00:00:00Z
2024-02-21T22:19:45Z
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dc.identifier.uri.fl_str_mv http://hdl.handle.net/10362/163895
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dc.relation.none.fl_str_mv 0007-0920
PURE: 5305964
https://doi.org/10.1038/bjc.2013.571
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