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http://hdl.handle.net/2445/178818
Title: | Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment |
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 |
Keywords: | Càncer Immunoteràpia Cèl·lules T Cancer Immunotherapy T cells |
Issue Date: | 9-Jun-2021 |
Publisher: | eLife Sciences Publications, Ltd |
Abstract: | 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. |
Note: | Reproducció del document publicat a: https://doi.org/10.7554/eLife.58688 |
It is part of: | eLife, 2021, vol. 10, num. e58688 |
URI: | http://hdl.handle.net/2445/178818 |
Related resource: | https://doi.org/10.7554/eLife.58688 |
Appears in Collections: | Publicacions de projectes de recerca finançats per la UE Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
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elife-58688-v2.pdf | 7.15 MB | Adobe PDF | View/Open |
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