{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T07:02:08Z","timestamp":1779778928608,"version":"3.53.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T00:00:00Z","timestamp":1779753600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>The therapeutic efficacy in malignant pleural mesothelioma (MPM) is severely hindered by its dense stromal barrier and immunosuppressive microenvironment. Although Tumor Treating Fields (TTFields) have demonstrated significant survival benefits in clinical trials, their underlying mechanisms extend well beyond simple mitotic arrest. This review delineates a \u201cmultidimensional biophysical remodeling\u201d atlas of TTFields in MPM. First, we highlight that TTFields physically disrupt actin-dependent intercellular \u201ctunneling nanotubes, \u201d thereby severing the tumor\u2019s communication and metabolic rescue networks. Second, physical stress downregulates the Fanconi Anemia-BRCA pathway, inducing a state of \u201cconditional BRCAness\u201d that specifically sensitizes tumors to DNA-damaging agents. Finally, this cascade triggers immunogenic cell death and orchestrates a chemokine storm, which is hypothesized to facilitate the conversion of the tumor microenvironment from an immune \u201ccold\u201d to a \u201chot\u201d phenotype. Collectively, by integrating the physical disintegration of subcellular structures with immunological remodeling, TTFields may offer a hypothetical theoretical framework for overcoming therapeutic resistance in MPM.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1782708","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T06:02:36Z","timestamp":1779775356000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor treating fields in malignant pleural mesothelioma: from cytoskeletal collapse to immunophenotypic conversion"],"prefix":"10.3389","volume":"17","author":[{"given":"Xiaofeng","family":"Ma","sequence":"first","affiliation":[{"name":"Emergency Center, The Second Hospital of Lanzhou University","place":["Lanzhou, Gansu, China"]},{"name":"School of Life Sciences and Technology, Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, Research Center of Special Environmental Biomechanics and Medical Engineering, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuo","family":"Zuo","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology, Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, Research Center of Special Environmental Biomechanics and Medical Engineering, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulong","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Technology, Key Laboratory for Space Biosciences & Biotechnology, Institute of Special Environmental Biophysics, Research Center of Special Environmental Biomechanics and Medical Engineering, Engineering Research Center of Chinese Ministry of Education for Biological Diagnosis, Treatment and Protection Technology and Equipment, Northwestern Polytechnical University","place":["Xi\u2019an, Shaanxi, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"An","sequence":"additional","affiliation":[{"name":"Emergency Center, The Second Hospital of Lanzhou University","place":["Lanzhou, Gansu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,26]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0063-2016","article-title":"Malignant pleural mesothelioma: an update on investigation, diagnosis and 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