Prostatectomy restores the maturation competence of blood dendritic cell precursors and reverses the abnormal expansion of regulatory T lymphocytes.
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(+)CD25(high)FoxP3(+)/CD4(+)CD25(high)CD127(low/-) 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 + CD25(high)FoxP3(+) or CD4(+)CD25(high)CD127(low/-), was significantly higher in pre-surgery patients than in NS (P = 0.0001 and 0.0003) and significant recovery of the CD4(+)CD25(high)CD127(low/-) (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.
Brusa
Davide
D
Laboratory of Tumor Immunology, San Giovanni Battista Hospital, Turin, Italy.
Carletto
Sara
S
Cucchiarale
Giuseppina
G
Gontero
Paolo
P
Greco
Alessandro
A
Simone
Mariagrazia
M
Ferrando
Ugo
U
Tizzani
Alessandro
A
Matera
Lina
L
D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D018122:B7-1 Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000601:surgery*; D054400:Receptors, CCR7 / Q000032:analysis; D050378:T-Lymphocytes, Regulatory / Q000502:physiology*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D054400:Receptors, CCR7; D000097802:CD83 Antigen; C515370:CCR7 protein, human