{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:14:05Z","timestamp":1791335645086,"version":"4.3.1"},"reference-count":68,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["GR-2013-02356568"],"award-info":[{"award-number":["GR-2013-02356568"]}]},{"name":"Italian Ministry of Health","award":["5 x 1000 Funds"],"award-info":[{"award-number":["5 x 1000 Funds"]}]},{"name":"Italian Ministry of Health","award":["Ricerca Corrente 2018-2021"],"award-info":[{"award-number":["Ricerca Corrente 2018-2021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Malignant mesothelioma (MM) is a rare tumor with an unfavorable prognosis. MM genesis involves asbestos-mediated local inflammation, supported by several cytokines, including IL-6. Recent data showed that targeting PD-1\/PD-L1 is an effective therapy in MM. Here, we investigated the effects of IL-6 trans-signaling and the IL-6-related cytokine IL-27 on human MM cells in vitro by Western blot analysis of STAT1\/3 phosphorylation. The effects on PD-L1 expression were tested by qRT-PCR and flow-cytometry and the release of soluble (s)PD-L1 by ELISA. We also measured the concentrations of sPD-L1 and, by multiplexed immunoassay, IL-6 and IL-27 in pleural fluids obtained from 77 patients in relation to survival. IL-27 predominantly mediates STAT1 phosphorylation and increases PD-L1 gene and surface protein expression and sPD-L1 release by human MM cells in vitro. IL-6 has limited activity, whereas a sIL-6R\/IL-6 chimeric protein mediates trans-signaling predominantly via STAT3 phosphorylation but has no effect on PD-L1 expression and release. IL-6, IL-27, and sPD-L1 are present in pleural fluids and show a negative correlation with overall survival, but only IL-27 shows a moderate albeit significant correlation with sPD-L1 levels. Altogether these data suggest a potential role of IL-27 in PD-L1-driven immune resistance in MM.<\/jats:p>","DOI":"10.3390\/cancers13164011","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T09:03:53Z","timestamp":1628499833000},"page":"4011","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["IL-27 Mediates PD-L1 Expression and Release by Human Mesothelioma Cells"],"prefix":"10.3390","volume":"13","author":[{"given":"Grazia","family":"Carbotti","sequence":"first","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatrice","family":"Dozin","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Martini","sequence":"additional","affiliation":[{"name":"Immunology Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Giordano","sequence":"additional","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Scordamaglia","sequence":"additional","affiliation":[{"name":"Department of Pneumology, Azienda Ospedaliera Villa Scassi, Corso O. Scassi 1, 16149 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-4951","authenticated-orcid":false,"given":"Michela","family":"Croce","sequence":"additional","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6445-8414","authenticated-orcid":false,"given":"Gilberto","family":"Filaci","sequence":"additional","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"},{"name":"Centre of Excellence for Biomedical Research and Department of Internal Medicine, University of Genoa, Via De Toni 14, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvano","family":"Ferrini","sequence":"additional","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"},{"name":"Department of Experimental Medicine, University of Genoa, Via L.B. Albertis 2, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4203-2022","authenticated-orcid":false,"given":"Marina","family":"Fabbi","sequence":"additional","affiliation":[{"name":"Biotherapies Unit, IRCCS Ospedale Policlinico San Martino, Largo R. Benzi 10, 16132 Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.12688\/f1000research.15512.2","article-title":"Factors Influencing Malignant Mesothelioma Survival: A Retrospective Review of the National Mesothelioma Virtual Bank Cohort","volume":"7","author":"Amin","year":"2018","journal-title":"F1000Research"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1016\/S1470-2045(17)30446-1","article-title":"Tremelimumab as Second-Line or Third-Line Treatment in Relapsed Malignant Mesothelioma (DETERMINE): A Multicentre, International, Randomised, Double-Blind, Placebo-Controlled Phase 2b Trial","volume":"18","author":"Maio","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S2213-2600(18)30151-6","article-title":"Tremelimumab Combined with Durvalumab in Patients with Mesothelioma (NIBIT-MESO-1): An Open-Label, Non-Randomised, Phase 2 Study","volume":"6","author":"Morra","year":"2018","journal-title":"Lancet Respir. 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