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BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes

BACKGROUND: The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T l...

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Autores principales: Chen, Yu-Li, Lin, Han-Wei, Chien, Chung-Liang, Lai, Yen-Ling, Sun, Wei-Zen, Chen, Chi-An, Cheng, Wen-Fang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868712/
https://www.ncbi.nlm.nih.gov/pubmed/31753019
http://dx.doi.org/10.1186/s40425-019-0744-4
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author Chen, Yu-Li
Lin, Han-Wei
Chien, Chung-Liang
Lai, Yen-Ling
Sun, Wei-Zen
Chen, Chi-An
Cheng, Wen-Fang
author_facet Chen, Yu-Li
Lin, Han-Wei
Chien, Chung-Liang
Lai, Yen-Ling
Sun, Wei-Zen
Chen, Chi-An
Cheng, Wen-Fang
author_sort Chen, Yu-Li
collection PubMed
description BACKGROUND: The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. METHODS: Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. RESULTS: The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19(hi) B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA(+)CD19(hi) B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients. CONCLUSIONS: BTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients. TRIAL REGISTRATION: The Trial Registration Number was NCT00854399.
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spelling pubmed-68687122019-12-12 BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes Chen, Yu-Li Lin, Han-Wei Chien, Chung-Liang Lai, Yen-Ling Sun, Wei-Zen Chen, Chi-An Cheng, Wen-Fang J Immunother Cancer Research Article BACKGROUND: The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. METHODS: Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. RESULTS: The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19(hi) B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA(+)CD19(hi) B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients. CONCLUSIONS: BTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients. TRIAL REGISTRATION: The Trial Registration Number was NCT00854399. BioMed Central 2019-11-21 /pmc/articles/PMC6868712/ /pubmed/31753019 http://dx.doi.org/10.1186/s40425-019-0744-4 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Chen, Yu-Li
Lin, Han-Wei
Chien, Chung-Liang
Lai, Yen-Ling
Sun, Wei-Zen
Chen, Chi-An
Cheng, Wen-Fang
BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title_full BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title_fullStr BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title_full_unstemmed BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title_short BTLA blockade enhances Cancer therapy by inhibiting IL-6/IL-10-induced CD19(high) B lymphocytes
title_sort btla blockade enhances cancer therapy by inhibiting il-6/il-10-induced cd19(high) b lymphocytes
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6868712/
https://www.ncbi.nlm.nih.gov/pubmed/31753019
http://dx.doi.org/10.1186/s40425-019-0744-4
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