TY - JOUR TI - Tumor stiffening reversion through collagen crosslinking inhibition improves T cell migration and anti-PD-1 treatment AU - Nicolas-Boluda, Alba AU - Vaquero, Javier AU - Vimeux, Lene AU - Guilbert, Thomas AU - Barrin, Sarah AU - Kantari-Mimoun, Chahrazade AU - Ponzo, Matteo AU - Renault, Gilles AU - Deptula, Piotr AU - Pogoda, Katarzyna AU - Bucki, Robert AU - Cascone, Ilaria AU - Courty, José AU - Fouassier, Laura AU - Gazeau, Florence AU - Donnadieu, Emmanuel A2 - Malissen, Bernard A2 - Ojala, Päivi M VL - 10 PY - 2021 DA - 2021/06/09 SP - e58688 C1 - eLife 2021;10:e58688 DO - 10.7554/eLife.58688 UR - https://doi.org/10.7554/eLife.58688 AB - 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. KW - tumor KW - extracellular matrix KW - T lymphocytes KW - immunotherapy KW - cell migration KW - stiffness JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -