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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Main Authors: Ramya Sivakumar, Marina Chan, Jiye Stella Shin, Nao Nishida-Aoki, Heidi L. Kenerson, Olivier Elemento, Himisha Beltran, Raymond Yeung, Taranjit S. Gujral
Format: Article
Language:English
Published: Taylor & Francis Group 2019-12-01
Series:OncoImmunology
Subjects:
Online Access:http://dx.doi.org/10.1080/2162402X.2019.1670019
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spelling doaj-9c72ba7fdcd04e50aee7360dda5c3acf2020-11-25T03:04:25ZengTaylor & Francis GroupOncoImmunology2162-402X2019-12-0181210.1080/2162402X.2019.16700191670019Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discoveryRamya Sivakumar0Marina Chan1Jiye Stella Shin2Nao Nishida-Aoki3Heidi L. Kenerson4Olivier Elemento5Himisha Beltran6Raymond Yeung7Taranjit S. Gujral8Fred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterFred Hutchinson Cancer Research CenterUniversity of Was hingtonWeill Cornell MedicineDana Farber Cancer Institute, Harvard Medical SchoolUniversity of Was hingtonFred Hutchinson Cancer Research CenterOrganotypic 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.http://dx.doi.org/10.1080/2162402X.2019.1670019tumor slicesimmuno-oncologyex vivo modelssyngeneic modelcancer
collection DOAJ
language English
format Article
sources DOAJ
author Ramya Sivakumar
Marina Chan
Jiye Stella Shin
Nao Nishida-Aoki
Heidi L. Kenerson
Olivier Elemento
Himisha Beltran
Raymond Yeung
Taranjit S. Gujral
spellingShingle Ramya Sivakumar
Marina Chan
Jiye Stella Shin
Nao Nishida-Aoki
Heidi L. Kenerson
Olivier Elemento
Himisha Beltran
Raymond Yeung
Taranjit S. Gujral
Organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
OncoImmunology
tumor slices
immuno-oncology
ex vivo models
syngeneic model
cancer
author_facet Ramya Sivakumar
Marina Chan
Jiye Stella Shin
Nao Nishida-Aoki
Heidi L. Kenerson
Olivier Elemento
Himisha Beltran
Raymond Yeung
Taranjit S. Gujral
author_sort Ramya Sivakumar
title 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_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_sort organotypic tumor slice cultures provide a versatile platform for immuno-oncology and drug discovery
publisher Taylor & Francis Group
series OncoImmunology
issn 2162-402X
publishDate 2019-12-01
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.
topic tumor slices
immuno-oncology
ex vivo models
syngeneic model
cancer
url http://dx.doi.org/10.1080/2162402X.2019.1670019
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