Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation

Y. Endo, R. Sakai, M. Ouchi, H. Onimatsu, M. Hioki, Shunsuke Kagawa, F. Uno, Y. Watanabe, Y. Urata, N. Tanaka, Toshiyoshi Fujiwara

Research output: Contribution to journalArticle

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Abstract

Dendritic cells (DCs) are the most potent antigen-presenting cells and acquire cellular antigens and danger signals from dying cells to initiate antitumor immune responses via direct cell-to-cell interaction and cytokine production. The optimal forms of tumor cell death for priming DCs for the release of danger signals are not fully understood. OBP-301 (Telomelysin) is a telomerase-specific replication-competent adenovirus that induces selective E1 expression and exclusively kills human cancer cells. Here, we show that OBP-301 replication produced the endogenous danger signaling molecule, uric acid, in infected human tumor cells, which in turn stimulated DCs to produce interferon-γ (IFN-γ) and interleukin 12 (IL-12). Subsequently, IFN-γ release upregulated the endogenous expression of the proteasome activator PA28 in tumor cells and resulted in the induction of cytotoxic T-lymphocytes. Our data suggest that virus-mediated oncolysis might be the effective stimulus for immature DCs to induce specific activity against human cancer cells.

Original languageEnglish
Pages (from-to)2375-2381
Number of pages7
JournalOncogene
Volume27
Issue number17
DOIs
Publication statusPublished - Apr 10 2008

Fingerprint

Cytotoxic T-Lymphocytes
Proteasome Endopeptidase Complex
Up-Regulation
Dendritic Cells
Viruses
Neoplasms
Interferons
Telomerase
Antigen-Presenting Cells
Interleukin-12
Uric Acid
Adenoviridae
Human Activities
Cell Communication
Cell Death
Cytokines
Antigens

Keywords

  • Adenovirus
  • Danger signal
  • Dendritic cell
  • Telomerase
  • Uric acid

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation. / Endo, Y.; Sakai, R.; Ouchi, M.; Onimatsu, H.; Hioki, M.; Kagawa, Shunsuke; Uno, F.; Watanabe, Y.; Urata, Y.; Tanaka, N.; Fujiwara, Toshiyoshi.

In: Oncogene, Vol. 27, No. 17, 10.04.2008, p. 2375-2381.

Research output: Contribution to journalArticle

Endo, Y, Sakai, R, Ouchi, M, Onimatsu, H, Hioki, M, Kagawa, S, Uno, F, Watanabe, Y, Urata, Y, Tanaka, N & Fujiwara, T 2008, 'Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation', Oncogene, vol. 27, no. 17, pp. 2375-2381. https://doi.org/10.1038/sj.onc.1210884
Endo, Y. ; Sakai, R. ; Ouchi, M. ; Onimatsu, H. ; Hioki, M. ; Kagawa, Shunsuke ; Uno, F. ; Watanabe, Y. ; Urata, Y. ; Tanaka, N. ; Fujiwara, Toshiyoshi. / Virus-mediated oncolysis induces danger signal and stimulates cytotoxic T-lymphocyte activity via proteasome activator upregulation. In: Oncogene. 2008 ; Vol. 27, No. 17. pp. 2375-2381.
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