FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

• Published in: The Prostate Vol. 78; no. 1; pp. 40 - 47
• Main Authors: Davidsson, Sabina, Andren, Ove, Ohlson, Anna‐Lena, Carlsson, Jessica, Andersson, Swen‐Olof, Giunchi, Francesca, Rider, Jennifer R., Fiorentino, Michelangelo
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.01.2018; John Wiley and Sons Inc
• Subjects: Bladder cancer; Cancer surgery; CD4 antigen; CD4+FOXP3+ Tregs; CD8 antigen; Forkhead Transcription Factors - metabolism; Foxp3 protein; Humans; Hyperplasia; Immunoregulation; Lag-3+ Tregs; Lymphocytes T; Male; Metastases; Original; Prostate - metabolism; Prostate - pathology; Prostate - surgery; Prostate cancer; prostate carcinoma; Prostatectomy; Prostatic intraepithelial neoplasia; Prostatic Intraepithelial Neoplasia - metabolism; Prostatic Intraepithelial Neoplasia - pathology; Prostatic Intraepithelial Neoplasia - surgery; Prostatic Neoplasms - metabolism; Prostatic Neoplasms - pathology; Prostatic Neoplasms - surgery; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - pathology; Urinary bladder; Urinary Bladder Neoplasms - metabolism; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - surgery; Urological surgery; CD4+FOXP3+ Tregs; prostate carcinoma; Lag-3+ Tregs
• ISSN: 0270-4137; 1097-0045; 1097-0045
• DOI: 10.1002/pros.23442

Background 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 (Tregs). In the present study we evaluated the prevalence of Treg 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. Methods 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+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established.