Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer

  • Authors: Masashi Yamamoto, Takashi Kamigaki, Kimihiro Yamashita, Yuichi Hori, Hiroshi Hasegawa, Daisuke Kuroda, Hiroaki Moriyama, Masao Nagata, Yonson Ku, Yoshikazu Kuroda
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  • Published online on: Saturday, August 1, 2009
  • Pages: 337-343
  • DOI: 10.3892/or_00000442

Abstract

Regulatory T cells (Tregs) play an important role in immunological self-tolerance and protect the host from autoimmune disease. However, in cancer immunity, Tregs might block anti-tumor immune responses. Therefore, the depletion of Tregs using a specific agent that suppresses its function or population, such as an anti-CD25 antibody, could promote anti-tumor immune responses. In the present study, a cytotoxicity assay, enzyme-linked immunosorbent spot (ELISPOT) assay and measuring cytokine secretion, were used to study the efficacy of Treg depletion by anti-CD25 antibody added to a dendritic cell/tumor cell (DC/TC) fusion hybrid vaccine in a murine pancreatic cancer model. All the mice treated with the combined therapy of fusion hybrid vaccine and Treg depletion rejected tumor growth in a challenging test, although the rejection rate was 20% both for mice that received the fusion hybrids alone or Treg depletion alone. In addition, combined therapy showed a significantly improved survival in comparison to other treatment or control groups. The NK cell activity for DC/TC fusion + Treg depletion was significantly higher than that for the other treatment groups. Cytotoxic T lymphocyte (CTL) activity for DC/TC could potentially be enhanced by the addition of Treg depletion therapy. The treatments including DC/TC fusion induced IFN-γ secreting effector cells in ELISPOT assays. Furthermore, a cytometric beads array assay used to measure cytokine secretion showed that DC/TC fusion + Treg depletion stimulated the highest levels of IFN-γ Th1/Th2 ratios and Th17. These results demonstrate that Treg depletion combined with DC/TC fusion hybrid vaccine enhanced the efficacy of immunotherapy in pancreatic cancer by activating CTLs and NK cells.
Journal Cover

August 2009
Volume 22 Issue 2

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

2013 Impact Factor: 2.191
Ranked #33/202 Oncology
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APA
Yamamoto, M., Kamigaki, T., Yamashita, K., Hori, Y., Hasegawa, H., Kuroda, D., Moriyama, H., Nagata, M., Ku, Y., & Kuroda, Y. (2009). Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer. Oncology Reports, 22(2), 337-343.
MLA
Yamamoto, Kamigaki, Yamashita, Hori, Hasegawa, Kuroda, Moriyama, Nagata, Ku, and Yoshikazu Kuroda. "Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer." Oncology Reports Oncology Reports 22.2 (2009): 337-343.
Chicago
Yamamoto, Kamigaki, Yamashita, Hori, Hasegawa, Kuroda, Moriyama, Nagata, Ku, and Yoshikazu Kuroda. "Enhancement of anti-tumor immunity by high levels of Th1 and Th17 with a combination of dendritic cell fusion hybrids and regulatory T cell depletion in pancreatic cancer." Oncology Reports Oncology Reports 22 no. 2 (2009): 337-343.