Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma

  • Authors:
    • Masanori Kawano
    • Ichiro Itonaga
    • Tatsuya Iwasaki
    • Hiroshi Tsumura
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  • Published online on: January 4, 2013     https://doi.org/10.3892/or.2013.2224
  • Pages: 1001-1006
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Abstract

Immunotherapy with tumor lysate-loaded dendritic cells (DCs) is one of the most promising strategies to induce antitumor immune responses. However, the antitumor activity of cytotoxic T cells may be restrained by their expression of the inhibitory T-cell coreceptor cytotoxic T lymphocyte antigen-4 (CTLA-4). By relieving this restraint, CTLA-4-blocking antibodies promote tumor rejection, but the full scope of their most suitable applications has yet to be fully determined. In the present study, we offer proof of a preclinical concept in a C3H mouse osteosarcoma (LM8) model that CTLA-4 blockade cooperates with cryotreated tumor lysate-pulsed DCs in a primary tumor to prevent the outgrowth of lung metastasis. To evaluate immune response activation, we established the following four groups of C3H mice (60 mice in total): i) control immunoglobulin G (IgG)-treated mice; ii) tumor lysate-pulsed DC-treated mice; iii) anti-CTLA-4 antibody-treated mice and iv) tumor lysate-pulsed DC- and anti-CTLA-4 antibody-treated mice. The mice that received the tumor lysate-pulsed DCs and anti-CTLA-4 antibody displayed reduced numbers of regulatory T lymphocytes and increased numbers of CD8+ T lymphocytes inside the metastatic tumor, inhibition of metastatic growth, a prolonged lifetime, reduced numbers of regulatory T lymphocytes in the spleen and high serum interferon-γ levels. Combining an anti-CTLA-4 antibody with tumor lysate-pulsed DCs enhanced the systemic immune response. To the best of our knowledge, these findings document for the first time an effect of the combination of tumor lysate-pulsed DCs and CTLA-4-blocking antibodies in osteosarcoma. We suggest that cryotreated tumor lysate-pulsed DCs, although insufficient on their own, may mediate the rejection of metastatic lesions and prevent recurrence of the disease when combined with CTLA-4 blockade in osteosarcoma patients in the clinical setting.
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March 2013
Volume 29 Issue 3

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

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Spandidos Publications style
Kawano M, Itonaga I, Iwasaki T and Tsumura H: Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma. Oncol Rep 29: 1001-1006, 2013
APA
Kawano, M., Itonaga, I., Iwasaki, T., & Tsumura, H. (2013). Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma. Oncology Reports, 29, 1001-1006. https://doi.org/10.3892/or.2013.2224
MLA
Kawano, M., Itonaga, I., Iwasaki, T., Tsumura, H."Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma". Oncology Reports 29.3 (2013): 1001-1006.
Chicago
Kawano, M., Itonaga, I., Iwasaki, T., Tsumura, H."Enhancement of antitumor immunity by combining anti-cytotoxic T lymphocyte antigen-4 antibodies and cryotreated tumor lysate-pulsed dendritic cells in murine osteosarcoma". Oncology Reports 29, no. 3 (2013): 1001-1006. https://doi.org/10.3892/or.2013.2224