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Depletion of CD4⁺CD25⁺ Regulatory T Cells Promotes a Tumor-Specific Immune Response in Pancreas Cancer–Bearing Mice

¹ Department of Surgery, Washington University School of Medicine, Box 8109, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA
² Department of Surgery, Divisions of General Surgery and Surgical Research, University of Basel, Spitalstrasse 21, 4031 Basel, Switzerland
³ Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri 63110, USA

Correspondence: Address correspondence and reprint requests to: David C. Linehan, MD; E-mail: linehand{at}wudosis.wustl.edu.

Background: Pancreas cancer–bearing mice have an increased prevalence of immunosuppressive CD4⁺CD25⁺ regulatory T cells (T_reg). Depletion of T_reg results in smaller tumors and prolonged host survival. The objective of this study was to evaluate the tumor-specific immune response after depletion of T_reg alone or in combination with a cancer vaccine.

Methods: Four groups of C57BL/6 mice were challenged with pancreas adenocarcinoma cells (Pan02). The mice received four combinations of antibody-mediated T_reg depletion and whole tumor cell vaccination: (1) no treatment, (2) T_reg depletion only, (3) vaccination only, or (4) T_reg depletion and vaccination. Splenocytes and lymphocytes from tumor-draining lymph nodes were analyzed for tumor-specific release of interferon by enzyme-linked immunosorbent spot assay.

Results: In T_reg-depleted and vaccinated mice, a strong statistical trend toward smaller tumors (P = .05) and longer survival (P = .054) was found compared with untreated mice. T_reg-depleted mice showed significantly more tumor-specific cells than undepleted mice (P = .02). The number of tumor-specific cells was significantly higher in tumor-draining lymph nodes than in the spleen (P = .002). Similarly, significantly more tumor-specific cells were found in spleens of T_reg-depleted and vaccinated mice than in vaccinated-only mice (P = .009).

Conclusions: Depletion of T_reg alone or in combination with a whole tumor cell vaccine promotes a tumor-specific immune response. Thus, strategies incorporating T_reg depletion might improve the efficacy of cancer vaccines.

Key Words: Tumor immunity • Regulatory T cells • Cancer vaccine • Pancreas cancer • Animal study

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