Poly(I:C) potentiates Bacillus Calmette–Guérin immunotherapy for bladder cancer

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• 作者：Cherifa Ayari ; Marjorie Besançon ; Alain Bergeron…
• 关键词：BCG ; Bladder cancer ; Immunotherapy ; Mouse model ; Poly(I ; C) ; TLR
• 刊名：Cancer Immunology, Immunotherapy
• 出版年：2016
• 出版时间：February 2016
• 年：2016
• 卷：65
• 期：2
• 页码：223-234
• 全文大小：1,038 KB
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• 作者单位：Cherifa Ayari (1)
  Marjorie Besançon (1)
  Alain Bergeron (1)
  Hélène LaRue (1)
  Vanessa Bussières (1)
  Yves Fradet (1)
  
  1. Centre de recherche sur le cancer de l’Université Laval, Centre de recherche du CHU de Québec-Université Laval, L’Hôtel-Dieu de Québec, 10 McMahon, Québec, G1R 3S1, Canada
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Cancer Research
  Immunology
  Oncology
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：1432-0851

文摘

Non-specific immunotherapy consisting of intravesical instillation of Bacillus Calmette–Guérin (BCG) is currently the best available treatment to prevent non-muscle-invasive bladder tumor recurrence and progression. This treatment however is suboptimal, and more effective immunotherapeutic approaches are needed. Toll-like receptors (TLRs) play a major role in the activation of the immune system in response to pathogens and danger signals but also in anti-tumor responses. We previously showed that human urothelial cells express functional TLRs and respond to TLR2 and TLR3 agonists. In this study, we analyzed the potential of polyinosinic:polycytidylic acid [poly(I:C)], a TLR3 agonist, to replace or complement BCG in the treatment of non-muscle-invasive bladder cancer. We observed that poly(I:C) had an anti-proliferative, cytotoxic, and apoptotic effect in vitro on two low-grade human bladder cancer cell lines, MGH-U3 and RT4. In MGH-U3 cells, poly(I:C) induced growth arrest at the G1-S transition. Poly(I:C) also increased the immunogenicity of MGH-U3 and RT4 cells, inducing the secretion of MHC class I molecules and of pro-inflammatory cytokines. By comparison, poly(I:C) had less in vitro impact on two high-grade human bladder cancer cell lines, 5637 and T24, and on MBT-2 murine high-grade bladder cancer cells. The latter can be used as an immunocompetent model of bladder cancer. The combination poly(I:C)/BCG was much more effective in reducing MBT-2 tumor growth in mice than either treatment alone. It completely cured 29 % of mice and also induced an immunological memory response. In conclusion, our study suggests that adding poly(I:C) to BCG may enhance the therapeutic effect of BCG. Keywords BCG Bladder cancer Immunotherapy Mouse model Poly(I:C) TLR