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Prostatectomy restores the maturation competence of blood dendritic cell precursors and reverses the abnormal expansion of regulatory T lymphocytes

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Abstract

OBJECTIVE

To verify the presence of deviated dendritic cell (DC) precursors and of suppressor lymphocytes (Treg) in tumor bearing prostate cancer (PCa) patients and to monitor the corrective effect of tumor ablation.

METHODS

Monocytes isolated from the blood of patients before and 1 month after prostatectomy were allowed to reach complete maturation (mDC) ex vivo in a clinical grade two-step process. T-regulatory cells were identified in the lymphocyte cell fraction by the CD4+CD25highFoxP3+/CD4+CD25highCD127low/− phenotype.

RESULTS

Despite loss of the monocytes marker CD14, cytokine-matured DCs of tumor bearing patients expressed lower levels of the costimulatory molecule CD80 and of the maturation markers CD83 and CCR7 compared to mDC of normal subjects (NS, P = 0.001, 0.001, and 0.008, respectively). Prostatectomy restored CD80, CD83, and CCR7 expression to values not different from those of NS (P = 0.15, 0.60, and 0.71) and significantly higher than those of the pre-surgery state (CD83, P = 0.0003 and CCR7, P = 0.002). The frequency of Tregs, identified as either CD4 + CD25highFoxP3+ or CD4+CD25highCD127low/−, was significantly higher in pre-surgery patients than in NS (P = 0.0001 and 0.0003) and significant recovery of the CD4+CD25highCD127low/− (P = 0.0005) was observed after surgery.

CONCLUSIONS

The presence of defective DC precursors and suppressor lymphocytes in the tumor-bearing, but not tumor-free stage, positions the latter as the ideal setting for clinical success of PCa vaccine therapy. Prostate 77:344–352, 2011. © 2010 Wiley-Liss, Inc.

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