{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:55:16Z","timestamp":1791327316193,"version":"4.3.1"},"reference-count":153,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T00:00:00Z","timestamp":1713398400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fulbright program AY2018 and American Society of Hematology (ASH) MHGA2023 Awards","award":["P01CA132714"],"award-info":[{"award-number":["P01CA132714"]}]},{"name":"Fulbright program AY2018 and American Society of Hematology (ASH) MHGA2023 Awards","award":["P01CA234212"],"award-info":[{"award-number":["P01CA234212"]}]},{"name":"Fulbright program AY2018 and American Society of Hematology (ASH) MHGA2023 Awards","award":["P50CA159981"],"award-info":[{"award-number":["P50CA159981"]}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P01CA132714"],"award-info":[{"award-number":["P01CA132714"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P01CA234212"],"award-info":[{"award-number":["P01CA234212"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"NCI","doi-asserted-by":"publisher","award":["P50CA159981"],"award-info":[{"award-number":["P50CA159981"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>The clinical management of bladder cancer continues to present significant challenges. Bacillus Calmette\u2013Gu\u00e9rin (BCG) immunotherapy remains the gold standard of treatment for non-muscle invasive bladder cancer (NMIBC), but many patients develop recurrence and progression to muscle-invasive disease (MIBC), which is resistant to BCG. This review focuses on the immune mechanisms mobilized by BCG in bladder cancer tumor microenvironments (TME), mechanisms of BCG resistance, the dual role of the BCG-triggered NFkB\/TNF\u03b1\/PGE2 axis in the regulation of anti-tumor and tumor-promoting aspects of inflammation, and emerging strategies to modulate their balance. A better understanding of BCG resistance will help develop new treatments and predictive biomarkers, paving the way for improved clinical outcomes in bladder cancer patients.<\/jats:p>","DOI":"10.3390\/cells13080699","type":"journal-article","created":{"date-parts":[[2024,4,18]],"date-time":"2024-04-18T07:55:54Z","timestamp":1713426954000},"page":"699","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Breaking Barriers: Modulation of Tumor Microenvironment to Enhance Bacillus Calmette\u2013Gu\u00e9rin Immunotherapy of Bladder Cancer"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9903-6657","authenticated-orcid":false,"given":"Omar M.","family":"Ibrahim","sequence":"first","affiliation":[{"name":"Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7025-3562","authenticated-orcid":false,"given":"Pawel","family":"Kalinski","sequence":"additional","affiliation":[{"name":"Department of Immunology, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14263, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1015","DOI":"10.1056\/NEJMoa1613683","article-title":"Pembrolizumab as second-line therapy for advanced urothelial carcinoma","volume":"376","author":"Bellmunt","year":"2017","journal-title":"N. 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