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 gamma 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.