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However, the mechanisms underlying the synergistic regulation of these two mechanical cues on the immunotherapy response in NSCLC cells remain poorly understood. In this study, it is demonstrated that both mechanical and biochemical activation of the mechanosensitive ion channel Piezo 1 induces nuclear translocation of YAP, thereby promoting an immunotherapy\u2010responsive tumor immune microenvironment (TIME) through enhanced expression of PD\u2010L1 and secretion of chemokine C\u2010X\u2010C ligand 10 (CXCL10, chemokine recruiting CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells) in NSCLC cells. The mathematical modeling further reveals that cyclic stretch modulates the PD\u2010L1\/CXCL10 response to ECM stiffness, shifting from a bimodal to a unimodal distribution. In a murine model of liver metastasis, the combination of Piezo 1 agonist with anti\u2010PD\u20101 therapy significantly improves the immunotherapy response, as evidenced by elevated PD\u2010L1 levels and increased CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell infiltration. These findings underscore the critical role of Piezo 1 in enhancing the immunotherapeutic response in NSCLC liver metastasis and highlight its potential as a therapeutic target.\n                  <\/jats:p>","DOI":"10.1002\/advs.202501335","type":"journal-article","created":{"date-parts":[[2025,6,30]],"date-time":"2025-06-30T00:14:44Z","timestamp":1751242484000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Piezo1 Activation Improves NSCLC Liver Metastasis Immunotherapy by Overriding Matrix Stiffness\u2010Mediated Bimodal PD\u2010L1\/CXCL10 Regulation"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2604-5648","authenticated-orcid":false,"given":"Tian","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Medical Oncology The Second Affiliated Hospital of Xi'an Jiaotong University  Xi'an 710004 P. R. 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