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Marked Expansion of CD11c+CD8+ T-Cells in Melanoma-bearing Mice Induced by Anti-4-1BB Monoclonal Antibody  

Ju, Seong-A (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Park, Sang-Min (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Lee, Sang-Chul (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Kwon, Byoung S. (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Kim, Byung-Sam (Department of Biological Sciences and Immunomodulation Research Center, University of Ulsan)
Publication Information
Molecules and Cells / v.24, no.1, 2007 , pp. 132-138 More about this Journal
Abstract
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 $IFN-{\gamma}$ 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, $IFN-{\gamma}$ 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.
Keywords
4-1BB; Anti-tummor immunity; Melanoma; Th1 cytokines;
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