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Annals of Surgical Oncology

, Volume 13, Issue 9, pp 1252–1258 | Cite as

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
Article

Abstract

Background

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.

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.

Keywords

Tumor immunity Regulatory T cells Cancer vaccine Pancreas cancer Animal study 

Notes

Acknowledgments

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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Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Carsten T. Viehl
    • 1
    • 2
  • Todd T. Moore
    • 1
  • Udaya K. Liyanage
    • 1
  • Daniel M. Frey
    • 1
    • 2
  • Jesmin P. Ehlers
    • 1
  • Timothy J. Eberlein
    • 1
    • 3
  • Peter S. Goedegebuure
    • 1
    • 3
  • David C. Linehan
    • 1
    • 3
  1. 1.Department of SurgeryWashington University School of MedicineSt. LouisUSA
  2. 2.Department of Surgery, Divisions of General Surgery and Surgical ResearchUniversity of BaselBaselSwitzerland
  3. 3.Alvin J. Siteman Cancer CenterWashington University School of MedicineSt. LouisUSA

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