Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma

  • Authors:
    • Masanori Kawano
    • Kazuhiro Tanaka
    • Ichiro Itonaga
    • Tatsuya Iwasaki
    • Masashi Miyazaki
    • Shinichi Ikeda
    • Hiroshi Tsumura
  • View Affiliations

  • Published online on: July 29, 2015     https://doi.org/10.3892/or.2015.4161
  • Pages: 1995-2001
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Abstract

We attempted to enhance the antitumor effects of tumor lysate-pulsed dendritic cells by eliminating regulatory T cells. The combinatorial effects of dendritic cells and agonist anti-glucocorticoid-induced tumor necrosis factor receptor (anti-GITR) antibodies were investigated with respect to enhancement of the systemic immune response, elimination of regulatory T cells, and inhibition of tumor growth. To determine whether the combination of dendritic cells and anti‑GITR antibodies could enhance systemic immune responses and inhibit primary tumor growth in a murine osteosarcoma (LM8) model. We established the following 4 groups of C3H mice (20 mice in total): i), control IgG-treated mice; ii), tumor lysate-pulsed dendritic cell‑treated mice; iii), agonist anti-GITR antibody-treated mice; and iv), agonist anti-GITR antibody- and tumor lysate-pulsed dendritic cell‑treated mice.The mice that received the agonist anti-GITR antibodies and tumor lysate-pulsed dendritic cells displayed inhibited primary growth, prolonged life time, reduced numbers of regulatory T lymphocytes in the spleen, elevated serum interferon-γ levels, increased number of CD8+ T lymphocytes. The mice that received combined therapy had reduced level of immunosuppressive cytokines in tumor tissue and serum. Combining agonist anti-GITR antibodies with tumor lysate-pulsed dendritic cells enhanced the systemic immune response. These findings provide further support for the continued development of agonist anti-GITR antibodies as an immunotherapeutic strategy for osteosarcoma. We suggest that our proposed immunotherapy could be developed further to improve osteosarcoma treatment.
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October-2015
Volume 34 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Kawano M, Tanaka K, Itonaga I, Iwasaki T, Miyazaki M, Ikeda S and Tsumura H: Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma. Oncol Rep 34: 1995-2001, 2015
APA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., & Tsumura, H. (2015). Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma. Oncology Reports, 34, 1995-2001. https://doi.org/10.3892/or.2015.4161
MLA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma". Oncology Reports 34.4 (2015): 1995-2001.
Chicago
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with anti-GITR antibody produce antitumor effects in osteosarcoma". Oncology Reports 34, no. 4 (2015): 1995-2001. https://doi.org/10.3892/or.2015.4161