{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:37:52Z","timestamp":1790739472736,"version":"4.1.0"},"reference-count":74,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T00:00:00Z","timestamp":1650931200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds National de la Recherche Scientifique (FNRS)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The composition of the tumor microenvironment (TME) mediates the outcome of chemo- and immunotherapies in malignant pleural mesothelioma (MPM). Tumor-associated macrophages (TAMs) and monocyte myeloid-derived immunosuppressive cells (M-MDSCs) constitute a major fraction of the TME. As central cells of the innate immune system, monocytes exert well-characterized functions of phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). The objective of this study was to evaluate the ability of monocytes to exert a direct cytotoxicity by cell-to-cell contact with MPM cells. The experimental model is based on cocultures between human blood-derived monocytes sorted by negative selection and mesothelioma cell lines. Data show (i) that blood-derived human monocytes induce tumor cell death by direct cell-to-cell contact, (ii) that VPA is a pharmacological enhancer of this cytotoxic activity, (iii) that VPA increases monocyte migration and their aggregation with MPM cells, and (iv) that the molecular mechanisms behind VPA modulation of monocytes involve a downregulation of the membrane receptors associated with the M2 phenotype, i.e., CD163, CD206, and CD209. These conclusions, thus, broaden our understanding about the molecular mechanisms involved in immunosurveillance of the tumor microenvironment and open new prospects for further improvement of still unsatisfactory MPM therapies<\/jats:p>","DOI":"10.3390\/cancers14092164","type":"journal-article","created":{"date-parts":[[2022,4,26]],"date-time":"2022-04-26T11:45:55Z","timestamp":1650973555000},"page":"2164","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["HDAC Inhibition with Valproate Improves Direct Cytotoxicity of Monocytes against Mesothelioma Tumor Cells"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0628-7642","authenticated-orcid":false,"given":"Clotilde","family":"Hoyos","sequence":"first","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Fontaine","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Rock","family":"Jacques","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Heinen","sequence":"additional","affiliation":[{"name":"Department of Pneumology\u2014Allergology, University Hospital, Sart-Tilman, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renaud","family":"Louis","sequence":"additional","affiliation":[{"name":"Department of Pneumology\u2014Allergology, University Hospital, Sart-Tilman, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Duysinx","sequence":"additional","affiliation":[{"name":"Department of Pneumology\u2014Allergology, University Hospital, Sart-Tilman, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Scherpereel","sequence":"additional","affiliation":[{"name":"Department of Pneumology and Thoracic Oncology, CHU Lille, 59037 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Wasielewski","sequence":"additional","affiliation":[{"name":"Department of Pneumology and Thoracic Oncology, CHU Lille, 59037 Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4629-5866","authenticated-orcid":false,"given":"Majeed","family":"Jamakhani","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0459-4005","authenticated-orcid":false,"given":"Malik","family":"Hamaidia","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0563-2213","authenticated-orcid":false,"given":"Luc","family":"Willems","sequence":"additional","affiliation":[{"name":"Molecular and Cellular Epigenetics, Interdisciplinary Cluster for Applied Genoproteomics (GIGA) and Molecular Biology, Teaching and Research Centre (TERRA), University of Li\u00e8ge, 4000 Liege, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S28","DOI":"10.21037\/tlcr.2019.11.11","article-title":"Epidemiology of mesothelioma in the 21st century in Europe and the United States, 40 years after restricted\/banned asbestos use","volume":"9","author":"Alpert","year":"2020","journal-title":"Transl. 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