Treg depletion followed by intracerebral CpG-ODN injection induce brain tumor rejection

J Neuroimmunol. 2014 Feb 15;267(1-2):35-42. doi: 10.1016/j.jneuroim.2013.12.005. Epub 2013 Dec 12.

Abstract

Using brain lymphoma model, we demonstrate that immunotherapy combining Treg depletion (using anti-CD25 mAb PC61) followed by intracranial CpG-ODN administration induced tumor rejection in all treated mice and led to the establishment of a memory antitumor immune response in 60% of them. This protective effect was associated with a recruitment of NK cells and, to a lesser extent, of dendritic cells, B cells and T lymphocytes. NK cell depletion abolished the protective effect of the treatment, confirming a major role of NK cells in brain tumor elimination. Each treatment used alone failed to protect brain tumor bearing mice, revealing the therapeutic benefit of combining Treg depletion and local CpG-ODN injection.

Keywords: CNS tumor; CpG-ODN; NK cells; PAMP; PRR; Treg; pathogen recognition receptor; pathogen-associated molecular pattern.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / therapeutic use*
  • Animals
  • Antibodies / toxicity
  • Antigens, Ly / immunology
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use
  • Brain Neoplasms / complications
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Etoposide / pharmacology
  • Etoposide / therapeutic use
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / drug effects
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Killer Cells, Natural / drug effects
  • Killer Cells, Natural / physiology
  • Lymphoma / complications
  • Lymphoma / drug therapy*
  • Lymphoma / metabolism
  • Lymphoma / pathology
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily B / immunology
  • Neoplasm Transplantation
  • Oligodeoxyribonucleotides / therapeutic use*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / physiology*
  • Time Factors
  • Toll-Like Receptor 9 / metabolism

Substances

  • Adjuvants, Immunologic
  • Antibodies
  • Antigens, Ly
  • Antineoplastic Agents, Phytogenic
  • CPG-oligonucleotide
  • Cytokines
  • Interleukin-2 Receptor alpha Subunit
  • Klrb1c protein, mouse
  • NK Cell Lectin-Like Receptor Subfamily B
  • Oligodeoxyribonucleotides
  • Toll-Like Receptor 9
  • Etoposide