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Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment
Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tum...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203293/ https://www.ncbi.nlm.nih.gov/pubmed/34106045 http://dx.doi.org/10.7554/eLife.58688 |
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author | Nicolas-Boluda, Alba Vaquero, Javier Vimeux, Lene Guilbert, Thomas Barrin, Sarah Kantari-Mimoun, Chahrazade Ponzo, Matteo Renault, Gilles Deptula, Piotr Pogoda, Katarzyna Bucki, Robert Cascone, Ilaria Courty, José Fouassier, Laura Gazeau, Florence Donnadieu, Emmanuel |
author_facet | Nicolas-Boluda, Alba Vaquero, Javier Vimeux, Lene Guilbert, Thomas Barrin, Sarah Kantari-Mimoun, Chahrazade Ponzo, Matteo Renault, Gilles Deptula, Piotr Pogoda, Katarzyna Bucki, Robert Cascone, Ilaria Courty, José Fouassier, Laura Gazeau, Florence Donnadieu, Emmanuel |
author_sort | Nicolas-Boluda, Alba |
collection | PubMed |
description | Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy. |
format | Online Article Text |
id | pubmed-8203293 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-82032932021-06-16 Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment Nicolas-Boluda, Alba Vaquero, Javier Vimeux, Lene Guilbert, Thomas Barrin, Sarah Kantari-Mimoun, Chahrazade Ponzo, Matteo Renault, Gilles Deptula, Piotr Pogoda, Katarzyna Bucki, Robert Cascone, Ilaria Courty, José Fouassier, Laura Gazeau, Florence Donnadieu, Emmanuel eLife Cancer Biology Only a fraction of cancer patients benefits from immune checkpoint inhibitors. This may be partly due to the dense extracellular matrix (ECM) that forms a barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous tumor microenvironments, we aimed to relate the rate of tumor stiffening with the remodeling of ECM architecture and to determine how these features affect intratumoral T cell migration. An ECM-targeted strategy, based on the inhibition of lysyl oxidase, was used. In vivo stiffness measurements were found to be strongly correlated with tumor growth and ECM crosslinking but negatively correlated with T cell migration. Interfering with collagen stabilization reduces ECM content and tumor stiffness leading to improved T cell migration and increased efficacy of anti-PD-1 blockade. This study highlights the rationale of mechanical characterizations in solid tumors to understand resistance to immunotherapy and of combining treatment strategies targeting the ECM with anti-PD-1 therapy. eLife Sciences Publications, Ltd 2021-06-09 /pmc/articles/PMC8203293/ /pubmed/34106045 http://dx.doi.org/10.7554/eLife.58688 Text en © 2021, Nicolas-Boluda et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Cancer Biology Nicolas-Boluda, Alba Vaquero, Javier Vimeux, Lene Guilbert, Thomas Barrin, Sarah Kantari-Mimoun, Chahrazade Ponzo, Matteo Renault, Gilles Deptula, Piotr Pogoda, Katarzyna Bucki, Robert Cascone, Ilaria Courty, José Fouassier, Laura Gazeau, Florence Donnadieu, Emmanuel Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title_full | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title_fullStr | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title_full_unstemmed | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title_short | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
title_sort | tumor stiffening reversion through collagen crosslinking inhibition improves t cell migration and anti-pd-1 treatment |
topic | Cancer Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8203293/ https://www.ncbi.nlm.nih.gov/pubmed/34106045 http://dx.doi.org/10.7554/eLife.58688 |
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