Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells

  • Authors:
    • Yasuto Akiyama
    • Chizu Nonomura
    • Ryota Kondou
    • Haruo Miyata
    • Tadashi Ashizawa
    • Chie Maeda
    • Koichi Mitsuya
    • Nakamasa Hayashi
    • Yoko Nakasu
    • Ken Yamaguchi
  • View Affiliations

  • Published online on: June 29, 2016     https://doi.org/10.3892/ijo.2016.3586
  • Pages: 1099-1107
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Abstract

Immune checkpoint antibody-mediated blockade has gained attention as a new cancer immunotherapy strategy. Accumulating evidence suggests that this therapy imparts a survival benefit to metastatic melanoma and non-small cell lung cancer patients. A substantial amount of data on immune checkpoint antibodies has been collected from clinical trials; however, the direct effect of the antibodies on human peripheral blood mononuclear cells (PBMCs) has not been exclusively investigated. In this study, we developed an anti-programmed death-1 (PD-1) antibody (with biosimilarity to nivolumab) and examined the effects of the antibody on PBMCs derived from cancer patients. Specifically, we investigated the effects of the anti-PD-1 antibody on proliferation, cytokine production, cytotoxic T lymphocytes (CTL) and regulatory T cells. These investigations yielded several important results. First, the anti-PD-1 antibody had no obvious effect on resting PBMCs; however, high levels of the anti-PD-1 antibody partly stimulated PBMC proliferation when accompanied by an anti-CD3 antibody. Second, the anti-PD-1 antibody restored the growth inhibition of anti-CD3 Ab-stimulated PBMCs mediated by PD-L1. Third, the anti-PD-1 antibody exhibited a moderate inhibitory effect on the induction of myeloid-derived suppressor cells (MDSCs) by anti-CD3 antibody stimulation. Additionally, the presence of the anti-PD-1 antibody promoted antigen-specific CTL induction, which suggests that combining anti-PD-1 antibody and conventional immunotherapy treatments may have beneficial effects. These results indicate that specific cellular immunological mechanisms are partly responsible for the antitumor effect exhibited by the anti-PD-1 antibody against advanced cancers in clinical trials.
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September 2016
Volume 49 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

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APA
Akiyama, Y., Nonomura, C., Kondou, R., Miyata, H., Ashizawa, T., Maeda, C. ... Yamaguchi, K. (2016). Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells. International Journal of Oncology, 49, 1099-1107. https://doi.org/10.3892/ijo.2016.3586
MLA
Akiyama, Y., Nonomura, C., Kondou, R., Miyata, H., Ashizawa, T., Maeda, C., Mitsuya, K., Hayashi, N., Nakasu, Y., Yamaguchi, K."Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells". International Journal of Oncology 49.3 (2016): 1099-1107.
Chicago
Akiyama, Y., Nonomura, C., Kondou, R., Miyata, H., Ashizawa, T., Maeda, C., Mitsuya, K., Hayashi, N., Nakasu, Y., Yamaguchi, K."Immunological effects of the anti-programmed death-1 antibody on human peripheral blood mononuclear cells". International Journal of Oncology 49, no. 3 (2016): 1099-1107. https://doi.org/10.3892/ijo.2016.3586