{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T12:24:08Z","timestamp":1789907048781,"version":"4.0.1"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Immunol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background<\/jats:title>\n            <jats:p>PD-1\/PD-L1 inhibitors have revolutionized urothelial carcinoma (UC) treatment; however, the effects of prior or concurrent therapies on PD-L1 regulation remain unclear. This study investigates whether enfortumab vedotin (EV), a nectin-4-targeting antibody-drug conjugate, modulates PD-L1 expression in UC cells, and explores the underlying molecular pathways.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>UC cell lines RT4 (high nectin-4 expression) and T24 (low nectin-4 expression) were treated with EV (10\u00a0\u00b5g\/ml) for 6, 12, or 24\u00a0h, followed by a 48-hour drug-free period. Protein and mRNA expression levels of PD-L1, NF-\u03baB, and STAT3 were quantified using western blotting and qRT-PCR.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>EV treatment upregulated PD-L1, NF-\u03baB, and STAT3 in a time-dependent manner, with a more pronounced effect observed in RT4 than in T24 cells. PD-L1 protein levels increased 0.761-fold (12\u00a0h) and 2.399-fold (24\u00a0h) in RT4, whereas T24 showed a decrease (0.517-fold at 12\u00a0h) or minimal change (0.006-fold at 24\u00a0h). NF-\u03baB expression increased 64.42-fold (12\u00a0h) and 97.03-fold (24\u00a0h) in RT4, compared to 1.251-fold (12\u00a0h) and 1.210-fold (24\u00a0h) in T24. STAT3 levels rose 2.334-fold (12\u00a0h) and 2.844-fold (24\u00a0h) in RT4, whereas T24 showed increases of 1.620-fold (12\u00a0h) and 1.379-fold (24\u00a0h). At the mRNA level (6\u00a0h post-treatment), PD-L1, NF-\u03baB, and STAT3 were upregulated by 1.228-, 1.332-, and 1.225-fold, respectively, in RT4 cells.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>EV is associated with increased PD-L1 expression, along with upregulation of NF-\u03baB and STAT3, suggesting a mechanistic link that may contribute to immune modulation in nectin-4-high bladder cancer cells. These findings highlight the need for combination strategies integrating EV with PD-1\/PD-L1 inhibitors to optimize therapeutic outcomes in UC.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/s12865-025-00751-2","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T12:40:01Z","timestamp":1758804001000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Enfortumab vedotin promotes PD-L1 expression in urothelial carcinoma via NF-\u03baB and STAT3 pathways highlighting mechanisms of immune evasion and potential for combination therapy"],"prefix":"10.1186","volume":"26","author":[{"given":"Hirohito","family":"Naito","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Taoka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akram","family":"Hossain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohei","family":"Abe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikio","family":"Sugimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"751_CR1","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. 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Because this is research using cell lines, ethical committee approval and informed consent are not required.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"70"}}