Marked expansion of CD11c+CD8+ T-cells in melanoma-bearing mice induced by anti-4-1BB monoclonal antibody

Mol Cells. 2007 Aug 31;24(1):132-8.


4-1BB (CD137), a member of the tumor necrosis factor receptor superfamily, is expressed on activated T-cells, and 4-1BB signaling due to interaction with 4-1BB ligand or ligation with anti-4-1BB monoclonal antibody (mAb) costimulates T cells. It has been shown that administration of anti-4-1BB mAb induces anti-tumor immunity in mice, but the nature of the cellular subsets responsible for this immunity is uncertain. In this study we found that anti-4-1BB mAb administration to B16F10 melanoma-bearing mice induced marked expansion of CD11c+CD8+ T-cells in parallel with suppression of pulmonary tumors. The mAb-treated mice produced higher levels of IFN- in their tumor tissues, spleen and lymph nodes than mice exposed to control antibody. When the CD11c+CD8+ T-cells were purified and re-stimulated in vitro, they produced high levels of the Th1 cytokines, IFN- and IL-2, but low levels of the Th2 cytokines, IL-4 and IL-10. Furthermore, they expressed high levels of 4-1BB and CD107a, a marker of activated cytotoxic T-lymphocytes. Our results suggest that CD11c+CD8+ T-cells play a role in the anti-tumor immunity induced by anti-4-1BB mAb.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / physiology*
  • CD11c Antigen / metabolism*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism
  • Interferon-gamma / biosynthesis
  • Lung Neoplasms / immunology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Melanoma, Experimental / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology*


  • Antibodies, Monoclonal
  • CD11c Antigen
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Interferon-gamma