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

Abstract

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. 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 γ by enzyme-linked immunosorbent spot assay. 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). 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.