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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
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.
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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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