Depletion of CD4+CD25+ Regulatory T Cells Promotes a Tumor-Specific Immune Response in Pancreas Cancer–Bearing Mice
Pancreas cancer–bearing mice have an increased prevalence of immunosuppressive CD4+CD25+ regulatory T cells (Treg). Depletion of Treg results in smaller tumors and prolonged host survival. The objective of this study was to evaluate the tumor-specific immune response after depletion of Treg 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 Treg depletion and whole tumor cell vaccination: (1) no treatment, (2) Treg depletion only, (3) vaccination only, or (4) Treg 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 Treg-depleted and vaccinated mice, a strong statistical trend toward smaller tumors (P = .05) and longer survival (P = .054) was found compared with untreated mice. Treg-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 Treg-depleted and vaccinated mice than in vaccinated-only mice (P = .009).
Depletion of Treg alone or in combination with a whole tumor cell vaccine promotes a tumor-specific immune response. Thus, strategies incorporating Treg depletion might improve the efficacy of cancer vaccines.
KeywordsTumor immunity Regulatory T cells Cancer vaccine Pancreas cancer Animal study
Supported in part by National Institutes of Health grants K08 CA87018-01 (D.C.L.) and T32 CA09621-11 (T.J.E.), as well as by grants from the Swiss National Science Foundation (81BE-067988) and the Regional Cancer League of Basel, Switzerland (C.T.V.)
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