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Article

Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma

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

    Affiliations: Department of Orthopaedic Surgery, Faculty of Medicine, Oita University, Yufu, Oita 879‑5593, Japan
  • Pages: 2169-2175
    |
    Published online on: February 2, 2016
       https://doi.org/10.3892/ol.2016.4175
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Abstract

The effects of dendritic cells (DCs) with low dose doxorubicin on the enhancement of the systemic immune response, including the effects on calreticulin (CRT) expression, heat shock protein 70 (HSP70) on the cell surface expression, and the enhancement of high mobility group box 1 (HMGB1) release from cancer cells, remain unclear. The present study investigated whether the combination of DCs and doxorubicin (ADM) induces immune cell death, and leads to tumor growth inhibition in a murine osteosarcoma model. To evaluate immune response activation in vivo, 4 groups of mice were established: i) untreated mice, ii) DC‑treated mice, iii) ADM‑treated mice, and iv) DC and ADM‑treated mice. Immunological cell death and CRT, HSP70, and HMGB1 expression levels were higher in doxorubicin-treated cells than those in untreated or those treated with DCs alone. NF-κB expression was higher in the DCs after ligand activation using CRT, HSP70, or HMGB1 in vitro. Mice treated with DCs and ADM displayed an increased number of CD8+ T‑lymphocytes within metastatic tumors and inhibition of metastatic growth. The expression of CRT and the release of HMGB1 from tumor tissues were increased in the ADM‑treated groups. Treatment with DCs and ADM resulted in the highest serum interferon‑γ levels. Combining ADM, which can induce immunogenic cell death, with DCs enhanced the systemic immune response. The findings of the present study provide further support for the continued development of antitumor agents that induce cell death and the immune response to target osteosarcoma.
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Copy and paste a formatted citation
Spandidos Publications style
Kawano M, Tanaka K, Itonaga I, Iwasaki T, Miyazaki M, Ikeda S and Tsumura H: Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. Oncol Lett 11: 2169-2175, 2016.
APA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., & Tsumura, H. (2016). Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. Oncology Letters, 11, 2169-2175. https://doi.org/10.3892/ol.2016.4175
MLA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma". Oncology Letters 11.3 (2016): 2169-2175.
Chicago
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma". Oncology Letters 11, no. 3 (2016): 2169-2175. https://doi.org/10.3892/ol.2016.4175
Copy and paste a formatted citation
x
Spandidos Publications style
Kawano M, Tanaka K, Itonaga I, Iwasaki T, Miyazaki M, Ikeda S and Tsumura H: Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. Oncol Lett 11: 2169-2175, 2016.
APA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., & Tsumura, H. (2016). Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma. Oncology Letters, 11, 2169-2175. https://doi.org/10.3892/ol.2016.4175
MLA
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma". Oncology Letters 11.3 (2016): 2169-2175.
Chicago
Kawano, M., Tanaka, K., Itonaga, I., Iwasaki, T., Miyazaki, M., Ikeda, S., Tsumura, H."Dendritic cells combined with doxorubicin induces immunogenic cell death and exhibits antitumor effects for osteosarcoma". Oncology Letters 11, no. 3 (2016): 2169-2175. https://doi.org/10.3892/ol.2016.4175
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