Clinical significance of intratumoral CD8+ regulatory T cells in prostate carcinoma.

ABSTRACT

OBJECTIVE: To explore Foxp3, a member of the forkhead box family of transcription factors, which is a major gene for regulatory T (Treg) cell development of CD4+CD25+ or CD8+CD25+ phenotype. STUDY DESIGN: We constructed tissue microarrays from 82 patients after radical prostatectomy (RP). Three cores of neoplastic tissue and 3 from normal/inflammatory tissue were taken. Sections were immunostained for Foxp3 and CD8. Numbers of Foxp3 and CD8 positive cells were counted. Serum prostate-specific antigen levels before and after RP, Gleason score (GS), surgical margin status and pathologic stage were available. RESULTS: Among 82 patients aged 55-76 years (mean 66.1, SD +/- 5.8), 64 (78%) were staged pT2 and 18 (22%) pT3. Twenty-nine patients (35%) had positive margins, 24 (29%) increasing prostate-specific antigen levels (biochemical relapse) 6 months to 2 years (SD +/- 24.8 months) after RP. GS was distributed as follows 41 (50%) patients with GS 6 (3+3), 34 (41%) with GS 7 [19 (3+4) and 15 (4+3)], 7 (9%) with GS > or = 8. In tumor cores, Foxp3 and CD8 counts correlated (p = 0.012). Foxp3 counts also correlated with biochemical relapse (p = 0.04). CONCLUSION: Treg cells were more common in cancer than in benign prostatic tissue. There are links between Foxp3 and CD8+ cells and between Foxp3 positive cells and biochemical relapse. Patients with prostate cancer show an immunosuppressive regulatory profile, including nonresponsive Tregs. It would be important to find mechanisms to target these cells for successful immunotherapy.