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Clinical importance of B7-H3 expression in human pancreatic cancer

BACKGROUND: B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the...

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Autores principales: Yamato, I, Sho, M, Nomi, T, Akahori, T, Shimada, K, Hotta, K, Kanehiro, H, Konishi, N, Yagita, H, Nakajima, Y
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778545/
https://www.ncbi.nlm.nih.gov/pubmed/19844235
http://dx.doi.org/10.1038/sj.bjc.6605375
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author Yamato, I
Sho, M
Nomi, T
Akahori, T
Shimada, K
Hotta, K
Kanehiro, H
Konishi, N
Yagita, H
Nakajima, Y
author_facet Yamato, I
Sho, M
Nomi, T
Akahori, T
Shimada, K
Hotta, K
Kanehiro, H
Konishi, N
Yagita, H
Nakajima, Y
author_sort Yamato, I
collection PubMed
description BACKGROUND: B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy. METHODS: We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model. RESULTS: Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8(+) T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity. CONCLUSION: Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease.
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spelling pubmed-27785452010-11-17 Clinical importance of B7-H3 expression in human pancreatic cancer Yamato, I Sho, M Nomi, T Akahori, T Shimada, K Hotta, K Kanehiro, H Konishi, N Yagita, H Nakajima, Y Br J Cancer Translational Therapeutics BACKGROUND: B7-H3 is a new member of the B7 ligand family and regulates T-cell responses in various conditions. However, the role of B7-H3 in tumour immunity is largely unknown. The purpose of this study was to evaluate the clinical significance of B7-H3 expression in human pancreatic cancer and the therapeutic potential for cancer immunotherapy. METHODS: We investigated B7-H3 expression in 59 patients with pancreatic cancer by immunohistochemistry and real-time PCR. Furthermore, we examined the anti-tumour effect of B7-H3-blocking monoclonal antibody in vivo in a murine pancreatic cancer model. RESULTS: Tumour-related B7-H3 expression was abundant in most human pancreatic cancer tissues and was significantly higher compared with that in non-cancer tissue or normal pancreas. Moreover, its expression was significantly more intense in cases with lymph node metastasis and advanced pathological stage. B7-H3 blockade promoted CD8(+) T-cell infiltration into the tumour and induced a substantial anti-tumour effect on murine pancreatic cancer. In addition, the combination of gemcitabine with B7-H3 blockade showed a synergistic anti-tumour effect without overt toxicity. CONCLUSION: Our data show for the first time that B7-H3 may have a critical role in pancreatic cancer and provide the rationale for developing a novel cancer immunotherapy against this fatal disease. Nature Publishing Group 2009-11-17 2009-10-20 /pmc/articles/PMC2778545/ /pubmed/19844235 http://dx.doi.org/10.1038/sj.bjc.6605375 Text en Copyright © 2009 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as 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 images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Yamato, I
Sho, M
Nomi, T
Akahori, T
Shimada, K
Hotta, K
Kanehiro, H
Konishi, N
Yagita, H
Nakajima, Y
Clinical importance of B7-H3 expression in human pancreatic cancer
title Clinical importance of B7-H3 expression in human pancreatic cancer
title_full Clinical importance of B7-H3 expression in human pancreatic cancer
title_fullStr Clinical importance of B7-H3 expression in human pancreatic cancer
title_full_unstemmed Clinical importance of B7-H3 expression in human pancreatic cancer
title_short Clinical importance of B7-H3 expression in human pancreatic cancer
title_sort clinical importance of b7-h3 expression in human pancreatic cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2778545/
https://www.ncbi.nlm.nih.gov/pubmed/19844235
http://dx.doi.org/10.1038/sj.bjc.6605375
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