The mechanical sensor PIEZO1 regulates the traction force that is critical for cytotoxic T cells to target tumour cells. This finding creates avenues for enhancing the efficacy of T cell-targeted immune therapies.
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References
Topalian, S. L., Taube, J. M., Anders, R. A. & Pardoll, D. M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 16, 275–287 (2016). A review article that presents the remaining questions regarding the optimal use of immune checkpoint blockade and biomarkers predicting therapeutic or adverse effects.
Huse, M. Mechanical forces in the immune system. Nat. Rev. Immunol. 17, 679–690 (2017). A review article that presents the argument that mechanical forces have crucial roles in immune cell activation and subsequent effector responses.
Mukhopadhyay, A. et al. trans-Endothelial neutrophil migration activates bactericidal function via Piezo1 mechanosensing. Immunity 57, 52–67 (2024). This paper reports that the increased membrane tension of neutrophils during transmigration triggers PIEZO1 signalling, leading to enhanced bactericidal activity.
Liu, Y. et al. Cell softness prevents cytolytic T-cell killing of tumor-repopulating cells. Cancer Res. 81, 476–488 (2021). This paper reports that soft tumour stem cells escape cytotoxic T cell attack by impairing the ‘hole drilling’ function of perforin.
Lv, J. et al. Cell softness regulates tumorigenicity and stemness of cancer cells. EMBO J. 40, e106123 (2021). This paper reports that softness is an inherent biomechanical feature of cancer stem cells.
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This is a summary of: Pang, R. et al. PIEZO1 mechanically regulates the antitumour cytotoxicity of T lymphocytes. Nat. Biomed. Eng. https://doi.org/10.1038/s41551-024-01188-5 (2024).
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Targeting the PIEZO1 pathway boosts T cell antitumour cytotoxicity. Nat. Biomed. Eng (2024). https://doi.org/10.1038/s41551-024-01189-4
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DOI: https://doi.org/10.1038/s41551-024-01189-4
