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Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition
Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients’ responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/o...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464600/ https://www.ncbi.nlm.nih.gov/pubmed/34564709 http://dx.doi.org/10.1038/s41420-021-00651-5 |
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author | Junk, David Krämer, Sebastian Broschewitz, Johannes Laura, Hennig Massa, Chiara Moulla, Yousef Hoang, Ngoc Anh Monecke, Astrid Eichfeld, Uwe Bechmann, Ingo Lordick, Florian Seliger, Barbara Kallendrusch, Sonja |
author_facet | Junk, David Krämer, Sebastian Broschewitz, Johannes Laura, Hennig Massa, Chiara Moulla, Yousef Hoang, Ngoc Anh Monecke, Astrid Eichfeld, Uwe Bechmann, Ingo Lordick, Florian Seliger, Barbara Kallendrusch, Sonja |
author_sort | Junk, David |
collection | PubMed |
description | Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients’ responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation. |
format | Online Article Text |
id | pubmed-8464600 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-84646002021-10-08 Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition Junk, David Krämer, Sebastian Broschewitz, Johannes Laura, Hennig Massa, Chiara Moulla, Yousef Hoang, Ngoc Anh Monecke, Astrid Eichfeld, Uwe Bechmann, Ingo Lordick, Florian Seliger, Barbara Kallendrusch, Sonja Cell Death Discov Article Despite novel immunotherapies being approved and established for the treatment of non-small cell lung cancer (NSCLC), ex vivo models predicting individual patients’ responses to immunotherapies are missing. Especially immune modulating therapies with moderate response rates urge for biomarkers and/or assays to determine individual prediction of treatment response and investigate resistance mechanisms. Here, we describe a standardized ex vivo tissue culture model to investigate individual tumor responses. NSCLC tissue cultures preserve morphological characteristics of the baseline tumor specimen for up to 12 days ex vivo and also maintain T-cell function for up to 10 days ex vivo. A semi-automated analysis of proliferating and apoptotic tumor cells was used to evaluate tissue responses to the PD-1 inhibitor nivolumab (n = 12), from which two cases could be successfully correlated to the clinical outcome. T-cell responses upon nivolumab treatment were investigated by flow cytometry and multispectral imaging. Alterations in the frequency of the Treg population and reorganization of tumor tissues could be correlated to nivolumab responsiveness ex vivo. Thus, our findings not only demonstrate the functionality of T cells in NSCLC slice cultures up to 10 days ex vivo, but also suggests this model for stratifying patients for treatment selection and to investigate in depth the tumor-associated T-cell regulation. Nature Publishing Group UK 2021-09-25 /pmc/articles/PMC8464600/ /pubmed/34564709 http://dx.doi.org/10.1038/s41420-021-00651-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access 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 http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Junk, David Krämer, Sebastian Broschewitz, Johannes Laura, Hennig Massa, Chiara Moulla, Yousef Hoang, Ngoc Anh Monecke, Astrid Eichfeld, Uwe Bechmann, Ingo Lordick, Florian Seliger, Barbara Kallendrusch, Sonja Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title | Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title_full | Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title_fullStr | Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title_full_unstemmed | Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title_short | Human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
title_sort | human tissue cultures of lung cancer predict patient susceptibility to immune-checkpoint inhibition |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464600/ https://www.ncbi.nlm.nih.gov/pubmed/34564709 http://dx.doi.org/10.1038/s41420-021-00651-5 |
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