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Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I\/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum\/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-na\u00efve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (\u00b13 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg\/m<jats:sup>2<\/jats:sup>) and pemetrexed (500mg\/m<jats:sup>2<\/jats:sup>) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous <jats:italic>Wilms\u2019 tumor 1<\/jats:italic> mRNA-electroporated dendritic cell (WT1\/DC) vaccination (8\u201310 x 10<jats:sup>6<\/jats:sup> cells\/vaccination). Additional atezolizumab (1680 mg) doses and\/or WT1\/DC vaccinations (8\u201310 x 10<jats:sup>6<\/jats:sup> cells\/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and\/or WT1\/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial\u2019s primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I\/II trial will evaluate whether addition of atezolizumab and WT1\/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.<\/jats:p>","DOI":"10.1371\/journal.pone.0307204","type":"journal-article","created":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T17:29:16Z","timestamp":1721064556000},"page":"e0307204","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Integration of the PD-L1 inhibitor atezolizumab and WT1\/DC vaccination into standard-of-care first-line treatment for patients with epithelioid malignant pleural mesothelioma\u2014Protocol of the Immuno-MESODEC study"],"prefix":"10.1371","volume":"19","author":[{"given":"Jolien","family":"Van den Bossche","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1434-0837","authenticated-orcid":true,"given":"Maxime","family":"De 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