{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T23:55:17Z","timestamp":1793145317776,"version":"4.5.0"},"reference-count":25,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Intravesical instillation of bacillus Calmette\u2013Gu\u00e9rin (BCG) is the standard treatment for bladder carcinoma in\u00a0situ (CIS); however, factors that predict its therapeutic efficacy have not been identified. We focused on immune cells infiltrating within 20\u2009\u03bcm of tumor cells and examined factors that predict the efficacy of intravesical BCG treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Formalin\u2010fixed, paraffin\u2010embedded tissue specimens from 82 patients with bladder CIS treated with intravesical BCG were used. Patients who relapsed after BCG treatment were grouped as non\u2010responders, and those who did not were grouped as responders. Tissue sections were immunostained for CD4, CD8, and forkhead box P3 (FOXP3), a marker of regulatory T cells (Tregs). The number of immune cells positive for the above markers present within 20\u2009\u03bcm of the lower edge of the basement membrane on which CIS is present was counted and compared between groups.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both the peritumoral Treg density and Treg+\/CD4+ cell ratio were significantly greater in nonresponders than in responders. The patients were divided into high and low groups based on Treg density and Treg+\/CD4+ cell ratio cut\u2010off values; recurrence\u2010free survival was significantly longer in the low group than in the high group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.005 and\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001, respectively).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The Treg density and Treg+\/CD4+ cell ratio within 20\u2009\u03bcm of bladder CIS may be useful predictors of therapeutic response to BCG.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iju.70044","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T06:59:37Z","timestamp":1741935577000},"page":"737-746","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Peritumoral Infiltration of Regulatory T Cells Reduces the Therapeutic Efficacy of Bacillus Calmette\u2013Gu\u00e9rin Therapy for Bladder Carcinoma In\u00a0Situ"],"prefix":"10.1111","volume":"32","author":[{"given":"Yusuke","family":"Fukiage","sequence":"first","affiliation":[{"name":"Department of Tumor Pathology, Faculty of Medical Sciences University of Fukui  Eiheiji Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akifumi","family":"Muramoto","sequence":"additional","affiliation":[{"name":"Department of Tumor Pathology, Faculty of Medical Sciences University of Fukui  Eiheiji 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