{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T21:01:46Z","timestamp":1793826106232,"version":"4.6.1"},"reference-count":150,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Associazione Italiana di Ricerca sul Cancro","award":["MFAG-2021 #26004"],"award-info":[{"award-number":["MFAG-2021 #26004"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) is a lethal and rare cancer, even if its incidence has continuously increased all over the world. Asbestos exposure leads to the development of mesothelioma through multiple mechanisms, including chronic inflammation, oxidative stress with reactive oxygen species (ROS) generation, and persistent aberrant signaling. Together, these processes, over the years, force normal mesothelial cells\u2019 transformation. Chronic inflammation supported by \u201cfrustrated\u201d macrophages exposed to asbestos fibers is also boosted by the release of pro-inflammatory cytokines, chemokines, growth factors, damage-associated molecular proteins (DAMPs), and the generation of ROS. In addition, the hypoxic microenvironment influences MPM and immune cells\u2019 features, leading to a significant rewiring of metabolism and phenotypic plasticity, thereby supporting tumor aggressiveness and modulating infiltrating immune cell responses. This review provides an overview of the complex tumor\u2013host interactions within the MPM tumor microenvironment at different levels, i.e., soluble factors, metabolic crosstalk, and oxidative stress, and explains how these players supporting tumor transformation and progression may become potential and novel therapeutic targets in MPM.<\/jats:p>","DOI":"10.3390\/cells12162048","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T10:20:16Z","timestamp":1691749216000},"page":"2048","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Chronic Inflammation, Oxidative Stress and Metabolic Plasticity: Three Players Driving the Pro-Tumorigenic Microenvironment in Malignant Mesothelioma"],"prefix":"10.3390","volume":"12","author":[{"given":"Irene","family":"Fiorilla","sequence":"first","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2891-1810","authenticated-orcid":false,"given":"Simona","family":"Martinotti","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto Maria","family":"Todesco","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0225-5763","authenticated-orcid":false,"given":"Gregorio","family":"Bonsignore","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. 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Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7600-8215","authenticated-orcid":false,"given":"Elia","family":"Ranzato","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-4175","authenticated-orcid":false,"given":"Valentina","family":"Audrito","sequence":"additional","affiliation":[{"name":"Department of Science and Technological Innovation (DISIT), University of Eastern Piedmont, 15121 Alessandria, Italy"},{"name":"Department of Integrated Activities Research and Innovation (DAIRI), Public Hospital Azienda Ospedaliera \u201cSS. Antonio e Biagio e Cesare Arrigo\u201d, 15121 Alessandria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/nrc.2017.42","article-title":"Novel Insights into Mesothelioma Biology and Implications for Therapy","volume":"17","author":"Yap","year":"2017","journal-title":"Nat. Rev. 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