| Autor: |
Alba Nicolas-Boluda, Javier Vaquero, Lene Vimeux, Thomas Guilbert, Sarah Barrin, Chahrazade Kantari-Mimoun, Matteo Ponzo, Gilles Renault, Piotr Deptula, Katarzyna Pogoda, Robert Bucki, Ilaria Cascone, José Courty, Laura Fouassier, Florence Gazeau, Emmanuel Donnadieu |
| Jazyk: |
angličtina |
| Rok vydání: |
2021 |
| Předmět: |
|
| Zdroj: |
eLife, Vol 10 (2021) |
| Druh dokumentu: |
article |
| ISSN: |
2050-084X |
| DOI: |
10.7554/eLife.58688 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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