{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T19:55:03Z","timestamp":1778788503678,"version":"3.51.4"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005026","name":"Stichting Tegen Kanker","doi-asserted-by":"publisher","award":["FA\/2014\/263"],"award-info":[{"award-number":["FA\/2014\/263"]}],"id":[{"id":"10.13039\/501100005026","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003130","name":"Fonds Wetenschappelijk Onderzoek","doi-asserted-by":"publisher","award":["1510215N"],"award-info":[{"award-number":["1510215N"]}],"id":[{"id":"10.13039\/501100003130","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003132","name":"Agentschap voor Innovatie door Wetenschap en Technologie","doi-asserted-by":"publisher","award":["141433"],"award-info":[{"award-number":["141433"]}],"id":[{"id":"10.13039\/501100003132","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In light of the promising results of immune checkpoint blockade (ICPB) in malignant pleural mesothelioma (MPM), we investigated the effect of different chemotherapeutic agents on the expression of immune checkpoints (ICPs) in order to rationally design a good treatment schedule for their combination with ICP blocking antibodies. Cisplatin, oxaliplatin and pemetrexed are interesting chemotherapeutic agents to combine with immunotherapy given their immunomodulatory capacities. We looked into cisplatin and pemetrexed because their combination is used as first-line treatment of MPM. Additionally, the effect of the immunogenic chemotherapeutic agent, oxaliplatin, was also studied. Three different MPM cell lines were used for representation of both epithelioid and sarcomatoid subtypes. The desired inhibitory concentrations of the chemotherapeutic agents were determined with the SRB-assay. Allogeneic co-cultures of MPM cells with healthy donor peripheral blood mononuclear cells (PBMC) were set up to assess the effect of these chemotherapeutic agents on the expression of ICPs (PD-1, LAG-3, TIM-3) and their ligands (PD-L1, PD-L2, galectin-9). Cisplatin might be a promising treatment to combine with ICP blocking antibodies since our MPM cell lines were most susceptible to this stand-alone treatment. We found that the expression of ICPs and their ligands on both MPM cells and PBMC was mostly downregulated or unaltered when treated with chemotherapeutic agents, though no clear trend could be determined.<\/jats:p>","DOI":"10.3390\/ijms20174182","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T10:54:53Z","timestamp":1566816893000},"page":"4182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Building a Bridge between Chemotherapy and Immunotherapy in Malignant Pleural Mesothelioma: Investigating the Effect of Chemotherapy on Immune Checkpoint Expression"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3173-0500","authenticated-orcid":false,"given":"Elly","family":"Marcq","sequence":"first","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5619-1913","authenticated-orcid":false,"given":"Jonas RM","family":"Van Audenaerde","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9999-6156","authenticated-orcid":false,"given":"Jorrit","family":"De Waele","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2873-3364","authenticated-orcid":false,"given":"Julie","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinthe","family":"Van Loenhout","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Cavents","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Pauwels","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"},{"name":"Department of Pathology, Antwerp University Hospital, 2650 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan P","family":"van Meerbeeck","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"},{"name":"Department of Pulmonology &amp; Thoracic Oncology, Antwerp University Hospital, 2650 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9255-3435","authenticated-orcid":false,"given":"Evelien LJ","family":"Smits","sequence":"additional","affiliation":[{"name":"Center for Oncological Research, University of Antwerp, 2000 Antwerp, Belgium"},{"name":"Center for Cell Therapy and Regenerative Medicine, Antwerp University Hospital, 2650 Antwerp, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/978-3-642-10862-4_6","article-title":"Mesothelioma and analysis of tissue fiber content","volume":"189","author":"Neumann","year":"2011","journal-title":"Recent Results Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"379","DOI":"10.2486\/indhealth.45.379","article-title":"Malignant mesothelioma: Global incidence and relationship with asbestos","volume":"45","author":"Bianchi","year":"2007","journal-title":"Ind. 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