{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:25:59Z","timestamp":1790616359309,"version":"4.1.0"},"reference-count":48,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2019,12,3]],"date-time":"2019-12-03T00:00:00Z","timestamp":1575331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08706"],"award-info":[{"award-number":["17K08706"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Diffuse malignant mesothelioma of the pleura (MPM) is a highly aggressive tumour that typically is associated with short survival. CD70 and CD27 belong to the tumour necrosis factor (TNF) and the TNF receptor (TNFR) superfamily, respectively. Under physiological conditions, the tightly regulated interaction between CD70 and CD27 plays a co\u2010stimulatory role in promoting T\u2010cell expansion and differentiation through the NF\u03baB pathway. Aberrantly high CD70 expression has been documented in haematological and solid malignancies in association with immune evasion in malignant cells. In this study, 172 well\u2010characterised primary diffuse MPM tumours including epithelioid (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009145), biphasic (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200915), and sarcomatoid (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200912) histotypes were evaluated immunohistochemically for CD70, CD27, CD3, CD4, CD8, CD56, PDCD1 (PD\u20101), and FOXP3 expression. Twenty per cent (34\/172) of the mesothelioma cells expressed CD70 on the cell membrane. Overall survival was significantly decreased in the cohort of patients with CD70\u2010expressing tumour cells (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01). Patients with MPM containing a higher number of CD3\n                    <jats:sup>+<\/jats:sup>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), CD4\n                    <jats:sup>+<\/jats:sup>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), CD8\n                    <jats:sup>+<\/jats:sup>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01), or FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.01) tumour\u2010infiltrating lymphoid cells (TILs) showed significantly worse clinical outcomes. As potential independent risk factors for MPM patients, multivariate Cox proportional hazards regression analysis revealed CD70 expression on mesothelioma cells [hazard ratio (HR) 2.25;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.010], higher FOXP3\n                    <jats:sup>+<\/jats:sup>\n                    TILs (HR 2.81;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.004), and higher CD3\n                    <jats:sup>+<\/jats:sup>\n                    TIL accumulation (HR 6.12;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). In contrast, as a potential independent favourable factor, higher CD27\n                    <jats:sup>+<\/jats:sup>\n                    TIL accumulation (HR 0.48;\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.037) was identified.\n                    <jats:italic>In vitro<\/jats:italic>\n                    experiments and an immunodeficient mouse model revealed that CD70 enhances the invasiveness of MPM cells through MET\u2013ERK axis activation. Further analyses in syngeneic mouse models demonstrated possible roles for CD70 in immune evasion. Collectively, these findings suggest that the CD70\u2013CD27 pathway enhances the malignant phenotypes of MPM and diminishes anti\u2010tumor immune response in patients with these neoplasms. These markers might be useful in MPM for prognostic evaluations as well as targeted therapeutics. \u00a9 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley &amp; Sons, Ltd.\n                  <\/jats:p>","DOI":"10.1002\/path.5361","type":"journal-article","created":{"date-parts":[[2019,10,22]],"date-time":"2019-10-22T12:47:40Z","timestamp":1571748460000},"page":"205-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":46,"title":["CD70 expression correlates with a worse prognosis in malignant pleural mesothelioma patients via immune evasion and enhanced invasiveness"],"prefix":"10.1002","volume":"250","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-8900","authenticated-orcid":false,"given":"Shingo","family":"Inaguma","sequence":"first","affiliation":[{"name":"Department of Pathology Aichi Medical University School of Medicine  Nagakute Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Lasota","sequence":"additional","affiliation":[{"name":"Laboratory of Pathology National Cancer Institute  Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Czapiewski","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology Medical University of Gdansk  Gdansk Poland"},{"name":"Department of Pathology Otto\u2010von\u2010Guericke University Magdeburg  Magdeburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata","family":"Langfort","sequence":"additional","affiliation":[{"name":"Department of Pathology National Tuberculosis and Lung Diseases Research Institute  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janusz","family":"Rys","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Centre of Oncology Maria Sklodowska\u2010Curie Memorial Institute, Krakow Branch  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Szpor","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology Jagiellonian University  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Waloszczyk","sequence":"additional","affiliation":[{"name":"Independent Laboratory of Pathology, Zdunomed  Szczecin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Oko\u0144","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology Jagiellonian University  Krakow Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wojciech","family":"Biernat","sequence":"additional","affiliation":[{"name":"Department of Pathomorphology Medical University of Gdansk  Gdansk Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David S","family":"Schrump","sequence":"additional","affiliation":[{"name":"Thoracic Surgery Branch National Cancer Institute  Bethesda MD 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