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Article Dans Une Revue eLife Année : 2021

Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment

Lene Vimeux
Thomas Guilbert
Sarah Barrin
  • Fonction : Auteur
Gilles Renault
  • Fonction : Auteur
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José Courty
Laura Fouassier
Florence Gazeau
Emmanuel Donnadieu

Résumé

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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hal-03443168 , version 1 (23-11-2021)

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Alba Nicolás-Boluda, Javier Vaquero, Lene Vimeux, Thomas Guilbert, Sarah Barrin, et al.. Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment. eLife, 2021, 10, ⟨10.7554/eLife.58688⟩. ⟨hal-03443168⟩
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