Depletion of regulatory T cells in a mouse experimental glioma model through anti-CD25 treatment results in the infiltration of non-immunosuppressive myeloid cells in the brain

Clin Dev Immunol. 2013;2013:952469. doi: 10.1155/2013/952469. Epub 2013 Apr 23.

Abstract

The recruitment and activation of regulatory T cells (Tregs) in the micro-environment of malignant brain tumors has detrimental effects on antitumoral immune responses. Hence, local elimination of Tregs within the tumor micro-environment represents a highly valuable tool from both a fundamental and clinical perspective. In the syngeneic experimental GL261 murine glioma model, Tregs were prophylactically eliminated through treatment with PC61, an anti-CD25 mAb. This resulted in specific elimination of CD4+CD25hiFoxp3+ Treg within brain-infiltrating lymphocytes and complete protection against subsequent orthotopic GL261 tumor challenge. Interestingly, PC61-treated mice also showed a pronounced infiltration of CD11b+ myeloid cells in the brain. Phenotypically, these cells could not be considered as Gr-1+ myeloid-derived suppressor cells (MDSC) but were identified as F4/80+ macrophages and granulocytes.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / pharmacology*
  • Brain / drug effects*
  • Brain / immunology
  • Brain / pathology
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / immunology
  • Brain Neoplasms / pathology
  • CD11b Antigen / genetics
  • CD11b Antigen / immunology
  • Cell Movement / drug effects
  • Cell Movement / immunology
  • Glioma / drug therapy*
  • Glioma / immunology
  • Glioma / pathology
  • Humans
  • Lymphocyte Depletion*
  • Lymphocytes, Tumor-Infiltrating / drug effects
  • Lymphocytes, Tumor-Infiltrating / immunology
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Mice
  • Myeloid Cells / drug effects*
  • Myeloid Cells / immunology
  • Myeloid Cells / pathology
  • Neoplasms, Experimental
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / pathology

Substances

  • Antibodies, Monoclonal
  • CD11b Antigen
  • PC61 monoclonal antibody