MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model

Abstract Bacillus Calmette-Guerin (BCG) is the only FDA approved first line therapy for patients with nonmuscle invasive bladder cancer. The purpose of this study is to better understand the role of innate immune pathways involved in BCG immunotherapy against murine bladder tumor. We first character...

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Autores principales:	Nina M. G. P. de Queiroz, Fabio V. Marinho, Ana Carolina V. S. C. de Araujo, Julia S. Fahel, Sergio C. Oliveira
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ca8937a512814b7b960d747443ddfd12
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spelling	oai:doaj.org-article:ca8937a512814b7b960d747443ddfd122021-12-02T14:53:48ZMyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model10.1038/s41598-021-95157-62045-2322https://doaj.org/article/ca8937a512814b7b960d747443ddfd122021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-95157-6https://doaj.org/toc/2045-2322Abstract Bacillus Calmette-Guerin (BCG) is the only FDA approved first line therapy for patients with nonmuscle invasive bladder cancer. The purpose of this study is to better understand the role of innate immune pathways involved in BCG immunotherapy against murine bladder tumor. We first characterized the immunological profile induced by the MB49 mouse urothelial carcinoma cell line. MB49 cells were not able to activate an inflammatory response (TNF-α, IL-6, CXCL-10 or IFN-β) after the stimulus with different agonists or BCG infection, unlike macrophages. Although MB49 cells are not able to induce an efficient immune response, BCG treatment could activate other cells in the tumor microenvironment (TME). We evaluated BCG intratumoral treatment in animals deficient for different innate immune molecules (STING−/−, cGAS−/−, TLR2−/−, TLR3−/−, TLR4−/−, TLR7−/−, TLR9−/−, TLR3/7/9−/−, MyD88−/−, IL-1R−/−, Caspase1/11−/−, Gasdermin-D−/− and IFNAR−/−) using the MB49 subcutaneous mouse model. Only MyD88−/− partially responded to BCG treatment compared to wild type (WT) mice, suggesting a role played by this adaptor molecule. Additionally, BCG intratumoral treatment regulates cellular infiltrate in TME with an increase of inflammatory macrophages, neutrophils and CD8+ T lymphocytes, suggesting an immune response activation that favors tumor remission in WT mice but not in MyD88−/−. The experiments using MB49 cells infected with BCG and co-cultured with macrophages also demonstrated that MyD88 is essential for an efficient immune response. Our data suggests that BCG immunotherapy depends partially on the MyD88-related innate immune pathway.Nina M. G. P. de QueirozFabio V. MarinhoAna Carolina V. S. C. de AraujoJulia S. FahelSergio C. OliveiraNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-19 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nina M. G. P. de Queiroz Fabio V. Marinho Ana Carolina V. S. C. de Araujo Julia S. Fahel Sergio C. Oliveira MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
description	Abstract Bacillus Calmette-Guerin (BCG) is the only FDA approved first line therapy for patients with nonmuscle invasive bladder cancer. The purpose of this study is to better understand the role of innate immune pathways involved in BCG immunotherapy against murine bladder tumor. We first characterized the immunological profile induced by the MB49 mouse urothelial carcinoma cell line. MB49 cells were not able to activate an inflammatory response (TNF-α, IL-6, CXCL-10 or IFN-β) after the stimulus with different agonists or BCG infection, unlike macrophages. Although MB49 cells are not able to induce an efficient immune response, BCG treatment could activate other cells in the tumor microenvironment (TME). We evaluated BCG intratumoral treatment in animals deficient for different innate immune molecules (STING−/−, cGAS−/−, TLR2−/−, TLR3−/−, TLR4−/−, TLR7−/−, TLR9−/−, TLR3/7/9−/−, MyD88−/−, IL-1R−/−, Caspase1/11−/−, Gasdermin-D−/− and IFNAR−/−) using the MB49 subcutaneous mouse model. Only MyD88−/− partially responded to BCG treatment compared to wild type (WT) mice, suggesting a role played by this adaptor molecule. Additionally, BCG intratumoral treatment regulates cellular infiltrate in TME with an increase of inflammatory macrophages, neutrophils and CD8+ T lymphocytes, suggesting an immune response activation that favors tumor remission in WT mice but not in MyD88−/−. The experiments using MB49 cells infected with BCG and co-cultured with macrophages also demonstrated that MyD88 is essential for an efficient immune response. Our data suggests that BCG immunotherapy depends partially on the MyD88-related innate immune pathway.
format	article
author	Nina M. G. P. de Queiroz Fabio V. Marinho Ana Carolina V. S. C. de Araujo Julia S. Fahel Sergio C. Oliveira
author_facet	Nina M. G. P. de Queiroz Fabio V. Marinho Ana Carolina V. S. C. de Araujo Julia S. Fahel Sergio C. Oliveira
author_sort	Nina M. G. P. de Queiroz
title	MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
title_short	MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
title_full	MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
title_fullStr	MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
title_full_unstemmed	MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
title_sort	myd88-dependent bcg immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/ca8937a512814b7b960d747443ddfd12
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_version_	1718389413200789504

MyD88-dependent BCG immunotherapy reduces tumor and regulates tumor microenvironment in bladder cancer murine model

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