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Published in:

01-09-2006

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

Authors: 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

Published in: Annals of Surgical Oncology | Issue 9/2006

Abstract

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 γ 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.

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Title: Depletion of CD4+CD25+ Regulatory T Cells Promotes a Tumor-Specific Immune Response in Pancreas Cancer–Bearing Mice
Authors: 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
Publication date: 01-09-2006
Publisher: Springer-Verlag
Published in: Annals of Surgical Oncology / Issue 9/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI: https://doi.org/10.1245/s10434-006-9015-y

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

Abstract

Background

Methods

Results

Conclusions

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Abstract

Background

Methods

Results

Conclusions

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