Depletion of CD4+CD25+ regulatory T cells promotes a tumor-specific immune response in pancreas cancer-bearing mice

Carsten T. Viehl, Todd T. Moore, Udaya K. Liyanage, Daniel M. Frey, Jesmin P. Ehlers, Timothy J. Eberlein, Peter S. Goedegebuure, David C. Linehan

Research output: Contribution to journalArticlepeer-review

107 Scopus citations

Abstract

Background: Pancreas cancer-bearing mice have an increased prevalence of immunosuppressive CD4+CD25+ regulatory T cells (T reg). 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. Methods: 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. Results: 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). Conclusions: 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. Published by Springer Science+Business Media, Inc.

Original languageEnglish
Pages (from-to)1252-1258
Number of pages7
JournalAnnals of Surgical Oncology
Volume13
Issue number9
DOIs
StatePublished - Sep 2006

Keywords

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

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