Depletion of CD4+CD25+ regulatory T cells enhances interleukin-2-induced antitumor immunity in a mouse model of colon adenocarcinoma

Cancer Sci. 2007 Mar;98(3):416-23. doi: 10.1111/j.1349-7006.2006.00385.x.


Interleukin 2 (IL)-2 induces antitumor immunity and clinical responses in melanoma and renal cell carcinoma. However, IL-2 also increases the number of CD4(+)CD25(+) regulatory T (Treg) cells that suppress antitumor immune responses. The aim of the present study was to elucidate the effect of depletion of Treg cells on IL-2-induced antitumor immunity. IL-2-transfected mouse colon adenocarcinoma (MC38/IL-2) cells were implanted subcutaneously or intrahepatically into male C57BL/6 mice, and tumor growth and the proportion of tumor-infiltrating lymphocytes with Treg-cell depletion in response to treatment with anti-CD25 monoclonal antibody (PC61) were determined. In mice treated with phosphate-buffered saline, 40-60% of MC38/IL-2 tumors were rejected. In contrast, all MC38/IL-2 tumors were rejected in mice treated with PC61. The number of tumor-infiltrating CD8(+) T cells in mice treated with PC61 was approximately twice that in mice treated with PBS. The numbers of tumor-infiltrating CD4(+) and natural killer cells were also increased significantly. To test the antimetastatic effects of IL-2 treatment in combination with Treg-cell depletion, human recombinant IL-2 (rIL-2) and PC61 were administered to mice implanted with MC38/mock cells in the spleen, and hepatic metastasis was investigated. The average liver weight in mice treated with rIL-2 plus PC61 was 1.04 +/- 0.03 g, less than that in mice treated with rIL-2 (2.04 +/- 0.51 g) or PC61 alone (1.81 +/- 0.38 g). We conclude that IL-2-induced antitumor immunity is enhanced by Treg-cell depletion and is due to expansion of the tumor-infiltrating cytotoxic CD8(+) T-cell population.

MeSH terms

  • Adenocarcinoma / immunology*
  • Animals
  • Cell Line, Tumor
  • Colonic Neoplasms / immunology*
  • Disease Models, Animal
  • Interleukin-2 / pharmacology*
  • Lymphocyte Depletion*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasms, Experimental / immunology*
  • Plasmids
  • T-Lymphocytes, Regulatory / immunology*
  • Transfection


  • Interleukin-2