{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:14:59Z","timestamp":1791314099803,"version":"4.3.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T00:00:00Z","timestamp":1509926400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"name":"Foundation for Medical Research at Orebro University Hospital"},{"name":"Lions Cancer Foundation"},{"name":"Orebro County Council Research Committee"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (T<jats:sub>regs<\/jats:sub>). In the present study we evaluated the prevalence of T<jats:sub>reg<\/jats:sub> populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> and CD8<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> in normal, PAH, PIN, and tumor lesions. A Friedma\u0144s test was used to investigate differences in the mean number of T<jats:sub>regs<\/jats:sub> across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In men with prostate cancer, similarly high numbers of stromal CD4<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> were identified in PAH and tumor, but CD4<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> were less common in PIN. Greater numbers of epithelial CD4+ T<jats:sub>regs<\/jats:sub> in normal prostatic tissue were positively associated with both Gleason score and pT\u2010stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> in the normal prostatic tissue counterpart.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4<jats:sup>+<\/jats:sup> T<jats:sub>regs<\/jats:sub> and indicate that transformation of the anti\u2010tumor immune response may be initiated even before the primary tumor is established.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.23442","type":"journal-article","created":{"date-parts":[[2017,11,6]],"date-time":"2017-11-06T07:59:18Z","timestamp":1509955158000},"page":"40-47","source":"Crossref","is-referenced-by-count":44,"title":["FOXP3<sup>+<\/sup> regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer"],"prefix":"10.1002","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2850-6009","authenticated-orcid":false,"given":"Sabina","family":"Davidsson","sequence":"first","affiliation":[{"name":"Department of Urology Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ove","family":"Andren","sequence":"additional","affiliation":[{"name":"Department of Urology Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna\u2010Lena","family":"Ohlson","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Pathology University Hospital \u00d6rebro \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Carlsson","sequence":"additional","affiliation":[{"name":"Department of Urology Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swen\u2010Olof","family":"Andersson","sequence":"additional","affiliation":[{"name":"Department of Urology Faculty of Medicine and Health \u00d6rebro University \u00d6rebro Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Giunchi","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Molecular Pathology Laboratory Addarii Institute of Oncology University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer R.","family":"Rider","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Boston University School of Public Health Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"Department of Hematology\u2010Oncology Molecular Pathology Laboratory Addarii Institute of Oncology University of Bologna Bologna Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.29210"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.25429"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djv224"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002371-200301000-00009"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1093"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.4.3.1644"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25947"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.10.7398"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0463.2010.02604.x"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2009.02.015"},{"key":"e_1_2_8_12_1","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.ejca.2012.11.035","article-title":"High 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