IFNAR blockade synergizes with oncolytic VSV to prevent virus-mediated PD-L1 expression and promote antitumor T cell activity.
- Resource Type
- Academic Journal
- Authors
- El-Sayes N; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Faculty of Health Science, McMaster University, Hamilton, ON, Canada.; Walsh S; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Vito A; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Faculty of Health Science, McMaster University, Hamilton, ON, Canada.; Reihani A; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada.; Ask K; Firestone Institute for Respiratory Health, McMaster University, Hamilton, ON, Canada.; Wan Y; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.; Mossman K; Department of Medicine, McMaster Immunology Research Centre, McMaster University, Hamilton, ON, Canada.
- Source
- Publisher: Cell Press Country of Publication: United States NLM ID: 101666776 Publication Model: eCollection Cited Medium: Print ISSN: 2372-7705 (Print) Linking ISSN: 23727705 NLM ISO Abbreviation: Mol Ther Oncolytics Subsets: PubMed not MEDLINE
- Subject
- Language
- English
- ISSN
- 2372-7705
Oncolytic virotherapies have shown excellent promise in a variety of cancers by promoting antitumor immunity. However, the effects of oncolytic virus-mediated type I interferon (IFN-I) production on antitumor immunity remain unclear. Recent reports have highlighted immunosuppressive functions of IFN-I in the context of checkpoint inhibitor and cell-based therapies. In this study, we demonstrate that oncolytic virus-induced IFN-I promotes the expression of PD-L1 in tumor cells and leukocytes in a IFN receptor (IFNAR)-dependent manner. Inhibition of IFN-I signaling using a monoclonal IFNAR antibody decreased IFN-I-induced PD-L1 expression and promoted tumor-specific T cell effector responses when combined with oncolytic virotherapy. Furthermore, IFNAR blockade improved therapeutic response to oncolytic virotherapy in a manner comparable with PD-L1 blockade. Our study highlights a critical immunosuppressive role of IFN-I on antitumor immunity and uses a combination strategy that improves the response to oncolytic virotherapy.
Competing Interests: The authors declare no competing interests.
(© 2022 The Author(s).)