Abstract
Disease progression is usually accompanied by changes in the biochemical composition of cells and tissues and their biophysical properties. For instance, hallmarks of cancer include the stiffening of tissues caused by extracellular matrix remodelling and the softening of individual cancer cells. In this context, accumulating evidence has shown that immune cells sense and respond to mechanical signals from the environment. However, the mechanisms regulating these mechanical aspects of immune surveillance remain partially understood. The growing appreciation for the ‘mechano-immunology’ field has urged researchers to investigate how immune cells sense and respond to mechanical cues in various disease settings, paving the way for the development of novel engineering strategies that aim at mechanically modulating and potentiating immune cells for enhanced immunotherapies. Recent pioneer developments in this direction have laid the foundations for leveraging ‘mechanical immunoengineering’ strategies to treat various diseases. This Review first outlines the mechanical changes occurring during pathological progression in several diseases, including cancer, fibrosis and infection. We next highlight the mechanosensitive nature of immune cells and how mechanical forces govern the immune responses in different diseases. Finally, we discuss how targeting the biomechanical features of the disease milieu and immune cells is a promising strategy for manipulating therapeutic outcomes.
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Acknowledgements
L.T. acknowledges the grant support from Swiss National Science Foundation (315230_204202, IZLCZ0_206035, CRSII5_205930), European Research Council under the ERC grant agreement MechanoIMM (805337), Swiss Cancer Research Foundation (KFS-4600-08-2018), Kristian Gerhard Jebsen Foundation, Anna Fuller Fund, Xtalpi Inc., and EPFL. J.G.G. acknowledges support from INSERM, University of Strasbourg and charities (Ligue contre le Cancer, Fondation ARC pour la recherche sur le cancer, Association Ruban Rose), which also support fellowships to V.M. and V.G. This work was also supported by grants from Plan Cancer to J.G.G. We apologize to the authors whose work could not be cited due to size constraints.
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V.M., V.G., L.B., W.L., L.T. and J.G.G. researched data for the paper. All authors made substantial contributions to the discussion of content, wrote the paper and reviewed and/or edited the paper before submission.
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L.T. is a co-founder, shareholder and advisor for Leman Biotech. The interests of L.T. were reviewed and managed by EPFL. The other authors declare no competing interests.
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Mittelheisser, V., Gensbittel, V., Bonati, L. et al. Evidence and therapeutic implications of biomechanically regulated immunosurveillance in cancer and other diseases. Nat. Nanotechnol. 19, 281–297 (2024). https://doi.org/10.1038/s41565-023-01535-8
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DOI: https://doi.org/10.1038/s41565-023-01535-8
