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

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 aggressive...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798967/
https://www.ncbi.nlm.nih.gov/pubmed/24064971
http://dx.doi.org/10.1038/bjc.2013.571
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author 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_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_sort Lima, L
collection PubMed
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.
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spelling pubmed-37989672014-10-15 Response of high-risk of recurrence/progression bladder tumours expressing sialyl-Tn and sialyl-6-T to BCG immunotherapy 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 Br J Cancer Clinical Study 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. Nature Publishing Group 2013-10-15 2013-09-24 /pmc/articles/PMC3798967/ /pubmed/24064971 http://dx.doi.org/10.1038/bjc.2013.571 Text en Copyright © 2013 Cancer Research UK http://creativecommons.org/licenses/by-nc-sa/3.0/ From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
spellingShingle Clinical Study
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
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
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_short 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
topic Clinical Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3798967/
https://www.ncbi.nlm.nih.gov/pubmed/24064971
http://dx.doi.org/10.1038/bjc.2013.571
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