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Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model

Bacillus Calmette-Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present st...

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Autores principales: Tan, Qing-Long, Zhou, Chang-Yuan, Cheng, Lin, Luo, Min, Liu, Chun-Ping, Xu, Wen-Xing, Zhang, Xian, Zeng, Xing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248479/
https://www.ncbi.nlm.nih.gov/pubmed/32319653
http://dx.doi.org/10.3892/mmr.2020.11090
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author Tan, Qing-Long
Zhou, Chang-Yuan
Cheng, Lin
Luo, Min
Liu, Chun-Ping
Xu, Wen-Xing
Zhang, Xian
Zeng, Xing
author_facet Tan, Qing-Long
Zhou, Chang-Yuan
Cheng, Lin
Luo, Min
Liu, Chun-Ping
Xu, Wen-Xing
Zhang, Xian
Zeng, Xing
author_sort Tan, Qing-Long
collection PubMed
description Bacillus Calmette-Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid (IL2Rg−/−) (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b(+) F4/80(+) after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro-differential genes Spi-1 proto-oncogene, early growth response protein 1, nuclear factor (NF)-κB and proto-oncogene c-Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor.
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spelling pubmed-72484792020-05-27 Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model Tan, Qing-Long Zhou, Chang-Yuan Cheng, Lin Luo, Min Liu, Chun-Ping Xu, Wen-Xing Zhang, Xian Zeng, Xing Mol Med Rep Articles Bacillus Calmette-Guérin (BCG) is considered to be a successful biotherapy for treating bladder cancer (BCa). However, the underlying mechanisms of BCG have not been completely clarified, to date. The role of macrophages in BCG therapy for BCa has still not been determined in vivo. In the present study, the role and potential mechanism of BCG (0.25, 1.25 and 6.25 µg/mouse; intravenous) immunotherapy for BCa was investigated in a NOD/scid (IL2Rg−/−) (NSI) mouse model by targeting macrophages in vivo. Notably, it was observed that NSI mice with T24 BCa cells displayed high levels of the macrophage marker CD11b(+) F4/80(+) after injection via the tail vein of live BCG, as well as a significant reduction in tumor volume. The levels of the inflammatory and macrophage maturation cytokines, such as tumor necrosis factor-α, interleukin (IL)-1β, IL-6, IL-12P70, TNF superfamily member 11 and monocyte chemotactic protein 1, were significantly increased in the serum and the tumor supernatant compared to that in normal control subjects. Furthermore, BCG promoted the expression of the pro-differential genes Spi-1 proto-oncogene, early growth response protein 1, nuclear factor (NF)-κB and proto-oncogene c-Fos in bone marrow. In conclusion, these observations indicate that the injection of live BCG can target macrophages against bladder tumor growth in vivo. The mechanism is likely related to the promotion of macrophage maturation, immune activation and increased numbers of macrophages infiltrating the bladder tumor. D.A. Spandidos 2020-07 2020-04-22 /pmc/articles/PMC7248479/ /pubmed/32319653 http://dx.doi.org/10.3892/mmr.2020.11090 Text en Copyright: © Tan et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Tan, Qing-Long
Zhou, Chang-Yuan
Cheng, Lin
Luo, Min
Liu, Chun-Ping
Xu, Wen-Xing
Zhang, Xian
Zeng, Xing
Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title_full Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title_fullStr Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title_full_unstemmed Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title_short Immunotherapy of Bacillus Calmette-Guérin by targeting macrophages against bladder cancer in a NOD/scid (IL2Rg-/−) mouse model
title_sort immunotherapy of bacillus calmette-guérin by targeting macrophages against bladder cancer in a nod/scid (il2rg-/−) mouse model
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248479/
https://www.ncbi.nlm.nih.gov/pubmed/32319653
http://dx.doi.org/10.3892/mmr.2020.11090
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