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bioRxiv · 10.1101/2025.09.28.678961

Matrix viscoelasticity regulates dendritic cell migration and immune priming

Jung, W.-H.·Humann, E.·Price, J. M.·Binenbaum, Y.·Haseki, A.·Iyer, S.·Mooney, D. J.
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Abstract

The tumor microenvironment shapes immune surveillance through its mechanical properties, yet the role of matrix viscoelasticity remains unclear. Here, we used a collagen system with tunable viscoelasticity to define how matrix relaxation directs dendritic cell (DC) behavior. Elastic matrices impaired DC migration by limiting actomyosin-driven collagen remodeling, thereby reducing DC-T cell encounters and weakening T cell priming, activation, proliferation, and tumor killing. Blocking DC migration in fast-relaxing gels recapitulated key aspects of the impaired T cell priming seen in elastic matrices. Prolonged confinement in elastic extracellular matrix induced a mechanomemory state, locking DCs into reduced motility even after transfer to viscoelastic environments, corresponding to altered chromatin accessibility. Finally, studies with patient-derived ependymoma samples confirmed these findings, identifying viscoelasticity as a barrier to antitumor immunity with implications for therapeutic intervention.

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Jung, W.-H., Humann, E., Price, J. M., Binenbaum, Y., Haseki, A., Iyer, S., Mooney, D. J.. 2025-09-30. Matrix viscoelasticity regulates dendritic cell migration and immune priming. https://doi.org/10.1101/2025.09.28.678961

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