REIC/Dkk-3 Gene therapy induces immunogenic cell death in a mouse model of malignant mesothelioma

Kenji Araki, Naoya Yamamuro, Nahoko Tomonobu, Hiromi Kumon

Research output: Contribution to journalArticlepeer-review

Abstract

Background/Aim: The adenovirus vector-carrying reduced expression in immortalized cell (REIC) gene (Ad-REIC) increases endoplasmic reticulum stress chaperone GRP78/BiP expression and induces the JNKmediated apoptotic pathway. We aimed to determine whether Ad-REIC-induced apoptotic cell death can trigger immunogenic cell death (ICD). Materials and Methods: We examined the emission of damage-associated molecular patterns in vitro and the vaccination effect in vivo. We determined the immunological changes in the tumour microenvironment by putative ICD inducers and the combined effects of immune checkpoint blockade therapies. Results: Ad-REIC induced the release of high-mobility group box 1 and adenosine triphosphate and the translocation of calreticulin in murine mesothelioma AB12 cells. The vaccination effect was elicited by Ad-REIC treatment in vivo. The effect of Ad-REIC was potentiated by anti-cytotoxic Tlymphocyte-associated protein 4 antibody treatment in a murine mesothelioma AB1-HA cell model. Conclusion: Ad-REIC induces ICD in malignant mesothelioma.

Original languageEnglish
Pages (from-to)4837-4855
Number of pages19
JournalAnticancer research
Volume41
Issue number10
DOIs
Publication statusPublished - Oct 2021

Keywords

  • Adenovirus vector
  • Anti-cancer immunity
  • Gene therapy
  • Immune checkpoint inhibitors
  • Immunogenic cell death
  • REIC

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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