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Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry
Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of i...
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/PMC8501076/ https://www.ncbi.nlm.nih.gov/pubmed/34625563 http://dx.doi.org/10.1038/s41467-021-26214-x |
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author | van Maldegem, Febe Valand, Karishma Cole, Megan Patel, Harshil Angelova, Mihaela Rana, Sareena Colliver, Emma Enfield, Katey Bah, Nourdine Kelly, Gavin Tsang, Victoria Siu Kwan Mugarza, Edurne Moore, Christopher Hobson, Philip Levi, Dina Molina-Arcas, Miriam Swanton, Charles Downward, Julian |
author_facet | van Maldegem, Febe Valand, Karishma Cole, Megan Patel, Harshil Angelova, Mihaela Rana, Sareena Colliver, Emma Enfield, Katey Bah, Nourdine Kelly, Gavin Tsang, Victoria Siu Kwan Mugarza, Edurne Moore, Christopher Hobson, Philip Levi, Dina Molina-Arcas, Miriam Swanton, Charles Downward, Julian |
author_sort | van Maldegem, Febe |
collection | PubMed |
description | Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells. |
format | Online Article Text |
id | pubmed-8501076 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-85010762021-10-22 Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry van Maldegem, Febe Valand, Karishma Cole, Megan Patel, Harshil Angelova, Mihaela Rana, Sareena Colliver, Emma Enfield, Katey Bah, Nourdine Kelly, Gavin Tsang, Victoria Siu Kwan Mugarza, Edurne Moore, Christopher Hobson, Philip Levi, Dina Molina-Arcas, Miriam Swanton, Charles Downward, Julian Nat Commun Article Mouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy. Here we present a workflow for studying the TME using imaging mass cytometry with a panel of 27 antibodies on frozen mouse tissues. We optimise and validate image segmentation strategies and automate the process in a Nextflow-based pipeline (imcyto) that is scalable and portable, allowing for parallelised segmentation of large multi-image datasets. With these methods we interrogate the remodelling of the TME induced by a KRAS G12C inhibitor in an immune competent mouse orthotopic lung cancer model, highlighting the infiltration and activation of antigen presenting cells and effector cells. Nature Publishing Group UK 2021-10-08 /pmc/articles/PMC8501076/ /pubmed/34625563 http://dx.doi.org/10.1038/s41467-021-26214-x 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 van Maldegem, Febe Valand, Karishma Cole, Megan Patel, Harshil Angelova, Mihaela Rana, Sareena Colliver, Emma Enfield, Katey Bah, Nourdine Kelly, Gavin Tsang, Victoria Siu Kwan Mugarza, Edurne Moore, Christopher Hobson, Philip Levi, Dina Molina-Arcas, Miriam Swanton, Charles Downward, Julian Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title | Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title_full | Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title_fullStr | Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title_full_unstemmed | Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title_short | Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
title_sort | characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501076/ https://www.ncbi.nlm.nih.gov/pubmed/34625563 http://dx.doi.org/10.1038/s41467-021-26214-x |
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