{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T01:14:04Z","timestamp":1791335644379,"version":"4.3.1"},"reference-count":50,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T00:00:00Z","timestamp":1675814400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07410"],"award-info":[{"award-number":["20K07410"]}],"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 CR"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Diffuse pleural mesothelioma (PM) is a highly aggressive tumour typically associated with short survival. Recently, the effectiveness of first\u2010line immune checkpoint inhibitors in patients with unresectable PM was reported. CD70\u2013CD27 signalling plays a co\u2010stimulatory role in promoting T cell expansion and differentiation through the nuclear factor \u03baB (NF\u2010\u03baB) pathway. Conversely, the PD\u2010L1 (CD274)\u2013PD\u20101 (PDCD1) pathway is crucial for the modulation of immune responses in normal conditions. Nevertheless, pathological activation of both the CD70\u2013CD27 and PD\u2010L1\u2013PD\u20101 pathways by aberrantly expressed CD70 and PD\u2010L1 participates in the immune evasion of tumour cells. In this study, 171 well\u2010characterised PMs including epithelioid (<jats:italic>n<\/jats:italic>\u00a0=\u00a0144), biphasic (<jats:italic>n<\/jats:italic>\u00a0=\u00a015), and sarcomatoid (<jats:italic>n<\/jats:italic>\u00a0=\u00a012) histotypes were evaluated immunohistochemically for CD70, PD\u2010L1, and immune cell markers such as CD3, CD4, CD8, CD56, PD\u20101, FOXP3, CD68, and CD163. Eight percent (14\/171) of mesotheliomas simultaneously expressed CD70 and PD\u2010L1 on the tumour cell membrane. PMs co\u2010expressing CD70 and PD\u2010L1 contained significantly higher numbers of CD8+ (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0016), FOXP3+ (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.00075), and CD163+ (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0011) immune cells within their microenvironments. Overall survival was significantly decreased in the cohort of patients with PM co\u2010expressing CD70 and PD\u2010L1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). <jats:italic>In vitro<\/jats:italic> experiments revealed that PD\u2010L1 and CD70 additively enhanced the motility and invasiveness of PM cells. In contrast, PM cell proliferation was suppressed by PD\u2010L1. PD\u2010L1 enhanced mesenchymal phenotypes such as N\u2010cadherin up\u2010regulation. Collectively, these findings suggest that CD70 and PD\u2010L1 both enhance the malignant phenotypes of PM and diminish anti\u2010tumour immune responses. Based on our observations, combination therapy targeting these signalling pathways might be useful in patients with PM.<\/jats:p>","DOI":"10.1002\/cjp2.310","type":"journal-article","created":{"date-parts":[[2023,2,8]],"date-time":"2023-02-08T22:38:51Z","timestamp":1675895931000},"page":"195-207","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["<scp>CD70<\/scp> and <scp>PD\u2010L1<\/scp> (<scp>CD274<\/scp>) co\u2010expression predicts poor clinical outcomes in patients with pleural mesothelioma"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8585-8900","authenticated-orcid":false,"given":"Shingo","family":"Inaguma","sequence":"first","affiliation":[{"name":"Department of Pathology Nagoya City University East Medical Center  Nagoya Japan"},{"name":"Department of Experimental Pathology and Tumor Biology Nagoya City University Graduate School of Medical Sciences  Nagoya 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