{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:48:56Z","timestamp":1787028536601,"version":"build-2736575974"},"reference-count":42,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T00:00:00Z","timestamp":1715644800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003196","name":"Italian Ministry of Health","doi-asserted-by":"publisher","award":["PSC SALUTE 2014-2020-POS2 \u201cCal-Hub-Ria\u201d"],"award-info":[{"award-number":["PSC SALUTE 2014-2020-POS2 \u201cCal-Hub-Ria\u201d"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Malignant pleural mesothelioma (MPM) remains an incurable disease. This is partly due to the lack of experimental models that fully recapitulate the complexity and heterogeneity of MPM, a major challenge for therapeutic management of the disease. In addition, the contribution of the MPM microenvironment is relevant for the adaptive response to therapy. We established mesothelioma patient-derived organoid (mPDO) cultures from MPM pleural effusions and tested their response to pemetrexed and cisplatin. We aimed to evaluate the contribution of mesothelioma-associated fibroblasts (MAFs) to the response to pemetrexed and cisplatin (P+C). Organoid cultures were obtained from eight MPM patients using specific growth media and conditions to expand pleural effusion-derived cells. Flow cytometry was used to verify the similarity of the organoid cultures to the original samples. MAFs were isolated and co-cultured with mPDOs, and the addition of MAFs reduced the sensitivity of mPDOs to P+C. Organoid formation and expression of cancer stem cell markers such as ABCG2, NANOG, and CD44 were altered by conditioned media from treated MAFs. We identified IL-6 as the major contributor to the attenuated response to chemotherapy. IL-6 secretion by MAFs is correlated with increased resistance of mPDOs to pemetrexed and cisplatin.<\/jats:p>","DOI":"10.3390\/ijms25105355","type":"journal-article","created":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T08:59:37Z","timestamp":1715677177000},"page":"5355","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mesothelioma-Associated Fibroblasts Modulate the Response of Mesothelioma Patient-Derived Organoids to Chemotherapy via Interleukin-6"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8129-6664","authenticated-orcid":false,"given":"Mario","family":"Cioce","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Medicine and Biotechnology, Department of Medicine, University of Campus-Biomedico of Rome, 00128 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council of Italy (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronica","family":"Gatti","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine and Biotechnology, Department of Medicine, University of Campus-Biomedico of Rome, 00128 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9242-6046","authenticated-orcid":false,"given":"Fabiana","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 81025 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4029-5837","authenticated-orcid":false,"given":"Noemi Maria","family":"Giorgiano","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unity, Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Marra","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine and Biotechnology, Department of Medicine, University of Campus-Biomedico of Rome, 00128 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council of Italy (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-9769","authenticated-orcid":false,"given":"Giuseppe","family":"Portella","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Naples Federico II, 81025 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-613X","authenticated-orcid":false,"given":"Alfonso","family":"Fiorelli","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Unity, Department of Translational Medical Sciences, University of Campania Luigi Vanvitelli, 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4740-6801","authenticated-orcid":false,"given":"Francesca","family":"Pentimalli","sequence":"additional","affiliation":[{"name":"Department of Medicine and Surgery, LUM University, 70010 Casamassima, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vito Michele","family":"Fazio","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Medicine and Biotechnology, Department of Medicine, University of Campus-Biomedico of Rome, 00128 Rome, Italy"},{"name":"Institute of Translational Pharmacology, National Research Council of Italy (CNR), 00133 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"107511","DOI":"10.1016\/j.rmed.2023.107511","article-title":"Comprehensive clinical overview of malignant pleural mesothelioma","volume":"222","author":"Khan","year":"2024","journal-title":"Respir. 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