In vivo depletion of DC impairs the anti-tumor effect of agonistic anti-CD137 mAb

Eur J Immunol. 2009 Sep;39(9):2424-36. doi: 10.1002/eji.200838958.


Anti-CD137 mAb are capable of inducing tumor rejection in several syngeneic murine tumor models and are undergoing clinical trials for cancer. The anti-tumor effect involves co-stimulation of tumor-specific CD8(+) T cells. Whether antigen cross-presenting DC are required for the efficacy of anti-CD137 mAb treatment has never been examined. Here we show that the administration of anti-CD137 mAb eradicates EG7-OVA tumors by a strictly CD8beta(+) T-cell-dependent mechanism that correlates with increased CTL activity. Ex vivo analyses to determine the identity of the draining lymph node cell type responsible for tumor antigen cross-presentation revealed that CD11c(+) cells, most likely DC, are the main players in this tumor model. A minute number of tumor cells, revealed by the presence of OVA cDNA, reach tumor-draining lymph nodes. Direct antigen presentation by tumor cells themselves also participates in anti-OVA CTL induction. Using CD11c diphtheria toxin receptor-green fluorescent protein-->C57BL/6 BM chimeric mice, which allow for sustained ablation of DC with diphtheria toxin, we confirmed the involvement of DC in tumor antigen cross-presentation in CTL induction against OVA(257-264) epitope and in the antitumor efficacy induced by anti-CD137 mAb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / therapeutic use*
  • Antigen Presentation / immunology
  • Antigens, Neoplasm / immunology
  • Cell Line, Tumor
  • Cross-Priming / immunology
  • Dendritic Cells / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • Ovalbumin / immunology
  • Peptide Fragments / immunology
  • T-Lymphocytes, Cytotoxic / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / agonists*
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology


  • Antibodies, Monoclonal
  • Antigens, Neoplasm
  • OVA-8
  • Peptide Fragments
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Ovalbumin