Sequential interferon β-cisplatin treatment enhances the surface exposure of calreticulin in cancer cells via an interferon regulatory factor 1-dependent manner

Pei Ming Yang, Yao Yu Hsieh, Jia Ling Du, Shih Chieh Yen, Chien Fu Hung

Research output: Contribution to journalArticle

Abstract

Immunogenic cell death (ICD) refers to a unique form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Accumulating evidence indicates that the efficacy of conventional anticancer agents relies on not only their direct cytostatic/cytotoxic effects but also the activation of antitumor ICD. Common anticancer ICD inducers include certain chemotherapeutic agents (such as anthracyclines, oxaliplatin, and bortezomib), radiotherapy, photodynamic therapy (PDT), and oncolytic virotherapies. However, most chemotherapeutic reagents are inefficient or fail to trigger ICD. Therefore, better understanding on the molecular determinants of chemotherapy-induced ICD will help in the development of more efficient combinational anticancer strategies through converting non- or relatively weak ICD inducers into bona fide ICD inducers. In this study, we found that sequential, but not concurrent, treatment of cancer cells with interferon β (IFN β), a type I IFN, and cisplatin (an inefficient ICD inducer) can enhance the expression of ICD biomarkers in cancer cells, including surface translocation of an endoplasmic reticulum (ER) chaperone, calreticulin (CRT), and phosphorylation of the eukaryotic translation initiation factor alpha (eIF2α). These results suggest that exogenous IFNβ may activate molecular determinants that convert cisplatin into an ICD inducer. Further bioinformatics and in vitro experimental analyses found that interferon regulatory factor 1 (IRF1) acted as an essential mediator of surface CRT exposure by sequential IFNβ-cisplatin combination. Our findings not only help to design more effective combinational anticancer therapy using IFNβ and cisplatin, but also provide a novel insight into the role of IRF1 in connecting the type I IFN responses and ICD.

Original languageEnglish (US)
Article number643
JournalBiomolecules
Volume10
Issue number4
DOIs
StatePublished - Apr 2020

Keywords

  • Bioinformatics
  • Chemotherapy
  • Endoplasmic reticulum stress
  • Immunogenic cell death
  • Interferon

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Sequential interferon β-cisplatin treatment enhances the surface exposure of calreticulin in cancer cells via an interferon regulatory factor 1-dependent manner'. Together they form a unique fingerprint.

Cite this