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Enhanced Functionality of CD4⁺CD25^highFoxP3⁺ Regulatory T Cells in the Peripheral Blood of Patients with Prostate Cancer

Authors' Affiliation: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland

Requests for reprints: Jeffrey Schlom, Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, NIH, 10 Center Drive, Room 8B09, Bethesda, MD 20892. Phone: 301-496-4343; Fax: 301-496-2756; E-mail: js141c{at}nih.gov.

Purpose: CD4⁺CD25^highFoxP3⁺ regulatory T cells (Treg) have been shown to inhibit the activation and function of T cells that participate in antigen-specific immune responses. Higher levels of Tregs have been reported in the peripheral blood of patients with several types of tumors. In this study, we investigated the number and functionality of CD4⁺CD25^highFoxP3⁺ Tregs in patients with prostate cancer (PCa), and their potential role in inhibiting antitumor immune responses.

Experimental Design: Levels of Tregs in the peripheral blood of healthy donors and patients with biochemically progressive, localized, and metastatic PCa were each measured by flow cytometry. The functional activity of Tregs was determined by their ability to suppress the proliferation of CD4⁺CD25^– T cells. Data were analyzed using Wilcoxon rank sum test and unpaired Student's t test.

Results: Although levels of Tregs in the peripheral blood of patients with PCa were not significantly higher than those in healthy donors, Tregs in patients with PCa had significantly greater suppressive functionality than Tregs from healthy donors (P < 0.05). Additionally, there was a direct correlation between the serum levels of prostaglandin E₂ and Treg functionality in patients with localized PCa, using Pearson's product-moment correlation coefficient (R).

Conclusions: These findings further show the potential importance of Tregs in modifying immune responses in patients with PCa. Although longer studies are necessary to confirm these findings, these studies also show for the first time the differences in Treg populations in patients with various stages of PCa, and thus, provide a basis for determining which PCa patient populations are best suited for immunotherapy trials involving the inhibition of Tregs.