title: CD4 helper T cells, CD8 cytotoxic T cells, and FOXP3(+) regulatory T cells with respect to lethal prostate cancer.
abstract: Prostate cancer represents a major contributor to cancer mortality, but the majority of men with prostate cancer will die of other causes. Thus, a challenge is identifying potentially lethal disease at diagnosis. Conflicting results have been reported when investigating the relationship between infiltration of lymphocytes and survival in prostate cancer. One of the mechanisms suggested is the recruitment of regulatory T cells (T(regs)), a subpopulation of T cells that have a role in promoting tumor growth. T(regs) counteract tumor rejection through suppressive functions on the anti-immune response but their prognostic significance is still unknown. We report here the results of a conducted case-control study nested in a cohort of men treated with transurethral resection of the prostate and diagnosed incidentally with prostate cancer. Cases are men who died of prostate cancer (n=261) and controls are men who survived >10 years after their diagnosis (n=474). Infiltration of both T(helper) and T(cytotoxic) cells was frequently observed and the majority of the T(regs) were CD4(+). T(helper) or T(cytotoxic) cells were not associated with lethal prostate cancer. However, we found a nearly twofold increased risk of lethal prostate cancer when comparing the highest with the lowest quartile of CD4(+) T(regs) cells (95% confidence interval: 1.3-2.9). Our conclusion is that men with greater numbers of CD4(+) T(regs) in their prostate tumor environment have an increased risk of dying of prostate cancer. Identification of CD4(+) T(regs) in tumor tissue may predict clinically relevant disease at time of diagnosis independently of other clinical factors.
authors.affiliation: Department of Urology, Örebro University Hospital, Örebro, Sweden. sabina.davidsson@orebroll.se
authors.forename: Sabina
authors.initials: S
authors.lastname: Davidsson
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Ohlson
authors.forename: Swen-Olof
authors.initials: SO
authors.lastname: Andersson
authors.forename: Katja
authors.initials: K
authors.lastname: Fall
authors.forename: Allison
authors.initials: A
authors.lastname: Meisner
authors.forename: Michelangelo
authors.initials: M
authors.lastname: Fiorentino
authors.forename: Ove
authors.initials: O
authors.lastname: Andrén
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Rider
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D033162:Incidental Findings; D016015:Logistic Models; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D009367:Neoplasm Staging; D016017:Odds Ratio; D011237:Predictive Value of Tests; D019048:Prostatic Intraepithelial Neoplasia / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D020728:Transurethral Resection of Prostate; D016896:Treatment Outcome; D057832:Watchful Waiting
chemical_list: D014408:Biomarkers, Tumor; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors