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 barrier for T cells. Comparing five preclinical mouse tumor models with heterogeneous microenvironments, we aimed relate rate stiffening remodeling ECM architecture and determine how these features affect intratumoral cell migration. An ECM-targeted strategy, based on inhibition lysyl oxidase, was used. In vivo stiffness measurements were found strongly correlated growth crosslinking but negatively Interfering collagen stabilization reduces content leading improved migration increased efficacy anti-PD-1 blockade. study highlights rationale mechanical characterizations in solid tumors understand resistance immunotherapy combining treatment strategies targeting therapy.