Open Access

Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes

  • Authors:
    • Yu Sawada
    • Toshiaki Yoshikawa
    • Manami Shimomura
    • Tatsuaki Iwama
    • Itaru Endo
    • Tetsuya Nakatsura
  • View Affiliations

  • Published online on: October 30, 2014     https://doi.org/10.3892/ijo.2014.2737
  • Pages: 28-36
  • Copyright: © Sawada et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Novel treatment modalities are required urgently in patients with hepatocellular carcinoma (HCC). A vaccine that induces cytotoxic T lymphocytes (CTLs) is an ideal strategy for cancer, and glypican-3 (GPC3) is a potential option for HCC. Blocking the programmed death-1 (PD-1)/PD-L1 pathway is a rational strategy to overcome tumor escape and tolerance toward CTLs. In the present study, we investigated whether anti-PD-1 blocking antibodies (αPD-1 Ab) enhanced the number of vaccine-induced peptide-specific CTLs in peripheral blood mononuclear cells (PBMCs) following the administration of GPC3 peptide vaccine to both patients and in a mouse model. The inhibitory receptor PD-1 was highly expressed in ex vivo GPC3-specific CTLs isolated from the PBMCs of vaccinated HCC patients. In vitro, interferon-γ induced PD-L1 expression in liver cancer cell lines. In addition, PD-1 blockade increased the number of GPC3-specific CTLs, which degranulate against liver cancer cell lines. In vivo experiments using tumor-bearing mouse models showed that the combination therapy of peptide vaccine and αPD-1 Ab suppressed tumor growth synergistically. PD-1 blockade increased the number of peptide-specific tumor-infiltrating T cells (TILs) and decreased the expression of inhibitory receptors on TILs. This study demonstrated that PD-1/PD-L1 blockade augmented the antitumor effects of a peptide vaccine by increasing the immune response of vaccine-induced CTLs, and provided a foundation for the clinical development of a combination therapy using a GPC3 peptide vaccine and αPD-1 Ab.
View Figures
View References

Related Articles

Journal Cover

January 2015
Volume 46 Issue 1

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Sawada, Y., Yoshikawa, T., Shimomura, M., Iwama, T., Endo, I., & Nakatsura, T. (2015). Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes. International Journal of Oncology, 46, 28-36. https://doi.org/10.3892/ijo.2014.2737
MLA
Sawada, Y., Yoshikawa, T., Shimomura, M., Iwama, T., Endo, I., Nakatsura, T."Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes". International Journal of Oncology 46.1 (2015): 28-36.
Chicago
Sawada, Y., Yoshikawa, T., Shimomura, M., Iwama, T., Endo, I., Nakatsura, T."Programmed death-1 blockade enhances the antitumor effects of peptide vaccine-induced peptide-specific cytotoxic T lymphocytes". International Journal of Oncology 46, no. 1 (2015): 28-36. https://doi.org/10.3892/ijo.2014.2737