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Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery

Organotypic tumor slices represent a physiologically-relevant culture system for studying the tumor microenvironment. Systematic characterization of the tumor slice culture system will enable its effective application for translational research. Here, using flow cytometry-based immunophenotyping, we...

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Autores principales: Sivakumar, Ramya, Chan, Marina, Shin, Jiye Stella, Nishida-Aoki, Nao, Kenerson, Heidi L., Elemento, Olivier, Beltran, Himisha, Yeung, Raymond, Gujral, Taranjit S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844320/
https://www.ncbi.nlm.nih.gov/pubmed/31741771
http://dx.doi.org/10.1080/2162402X.2019.1670019
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author Sivakumar, Ramya
Chan, Marina
Shin, Jiye Stella
Nishida-Aoki, Nao
Kenerson, Heidi L.
Elemento, Olivier
Beltran, Himisha
Yeung, Raymond
Gujral, Taranjit S.
author_facet Sivakumar, Ramya
Chan, Marina
Shin, Jiye Stella
Nishida-Aoki, Nao
Kenerson, Heidi L.
Elemento, Olivier
Beltran, Himisha
Yeung, Raymond
Gujral, Taranjit S.
author_sort Sivakumar, Ramya
collection PubMed
description Organotypic tumor slices represent a physiologically-relevant culture system for studying the tumor microenvironment. Systematic characterization of the tumor slice culture system will enable its effective application for translational research. Here, using flow cytometry-based immunophenotyping, we performed a comprehensive characterization of the immune cell composition in organotypic tumor slices prepared from four syngeneic mouse tumor models and a human liver tumor. We found that the immune cell compositions of organotypic tumor slices prepared on the same day as the tumor cores were harvested are similar. Differences were primarily observed in the lymphocyte population of a clinical hepatocellular carcinoma case. Viable populations of immune cells persisted in the tumor slices for 7 days. Despite some changes in the immune cell populations, we showed the utility of mouse tumor slices for assessing responses to immune-modulatory agents. Further, we demonstrated the ability to use patient-derived xenograft tumor slices for assessing responses to targeted and cytotoxic drugs. Overall, tumor slices provide a broadly useful platform for studying the tumor microenvironment and evaluating the preclinical efficacy of cancer therapeutics.
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spelling pubmed-68443202019-11-18 Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery Sivakumar, Ramya Chan, Marina Shin, Jiye Stella Nishida-Aoki, Nao Kenerson, Heidi L. Elemento, Olivier Beltran, Himisha Yeung, Raymond Gujral, Taranjit S. Oncoimmunology Original Research Organotypic tumor slices represent a physiologically-relevant culture system for studying the tumor microenvironment. Systematic characterization of the tumor slice culture system will enable its effective application for translational research. Here, using flow cytometry-based immunophenotyping, we performed a comprehensive characterization of the immune cell composition in organotypic tumor slices prepared from four syngeneic mouse tumor models and a human liver tumor. We found that the immune cell compositions of organotypic tumor slices prepared on the same day as the tumor cores were harvested are similar. Differences were primarily observed in the lymphocyte population of a clinical hepatocellular carcinoma case. Viable populations of immune cells persisted in the tumor slices for 7 days. Despite some changes in the immune cell populations, we showed the utility of mouse tumor slices for assessing responses to immune-modulatory agents. Further, we demonstrated the ability to use patient-derived xenograft tumor slices for assessing responses to targeted and cytotoxic drugs. Overall, tumor slices provide a broadly useful platform for studying the tumor microenvironment and evaluating the preclinical efficacy of cancer therapeutics. Taylor & Francis 2019-10-10 /pmc/articles/PMC6844320/ /pubmed/31741771 http://dx.doi.org/10.1080/2162402X.2019.1670019 Text en © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.
spellingShingle Original Research
Sivakumar, Ramya
Chan, Marina
Shin, Jiye Stella
Nishida-Aoki, Nao
Kenerson, Heidi L.
Elemento, Olivier
Beltran, Himisha
Yeung, Raymond
Gujral, Taranjit S.
Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title_full Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title_fullStr Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title_full_unstemmed Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title_short Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
title_sort organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844320/
https://www.ncbi.nlm.nih.gov/pubmed/31741771
http://dx.doi.org/10.1080/2162402X.2019.1670019
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