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

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Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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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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Authors and Affiliations

  1. Department of Surgery, Washington University School of Medicine, Box 8109, 660 S. Euclid Ave., St. Louis, Missouri, 63110, USA

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

  2. Department of Surgery, Divisions of General Surgery and Surgical Research, University of Basel, Spitalstrasse 21, 4031, Basel, Switzerland

    Carsten T. Viehl MD & Daniel M. Frey MD

  3. Alvin J. Siteman Cancer Center, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, Missouri, 63110, USA

    Timothy J. Eberlein MD, Peter S. Goedegebuure PhD & David C. Linehan MD

Authors
  1. Carsten T. Viehl MD
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  2. Todd T. Moore BS
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  3. Udaya K. Liyanage MD
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  4. Daniel M. Frey MD
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  5. Jesmin P. Ehlers BS
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  6. Timothy J. Eberlein MD
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  7. Peter S. Goedegebuure PhD
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  8. David C. Linehan MD
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Correspondence to David C. Linehan MD.

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Viehl, C.T., Moore, T.T., Liyanage, U.K. et al. Depletion of CD4+CD25+ Regulatory T Cells Promotes a Tumor-Specific Immune Response in Pancreas Cancer–Bearing Mice. Ann Surg Oncol 13, 1252–1258 (2006). https://doi.org/10.1245/s10434-006-9015-y

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  • DOI: https://doi.org/10.1245/s10434-006-9015-y

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