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

Ann Surg Oncol. 2006 Sep;13(9):1252-8. doi: 10.1245/s10434-006-9015-y. Epub 2006 Sep 3.


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 gamma 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / metabolism*
  • Cancer Vaccines / therapeutic use
  • Female
  • Granulocyte-Macrophage Colony-Stimulating Factor / administration & dosage
  • Interferon-gamma / metabolism
  • Lymph Nodes / immunology
  • Lymphocyte Activation
  • Lymphocyte Depletion*
  • Mice
  • Mice, Inbred C57BL
  • Pancreatic Neoplasms / immunology*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Receptors, Interleukin-2 / immunology
  • Receptors, Interleukin-2 / metabolism*
  • Spleen / immunology
  • Spleen / metabolism
  • Spleen / pathology
  • Survival Rate
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / pathology


  • Antibodies, Monoclonal
  • Cancer Vaccines
  • Receptors, Interleukin-2
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor