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IFNAR blockade synergizes with oncolytic VSV to prevent virus-mediated PD-L1 expression and promote antitumor T cell activity.


ABSTRACT: 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.

SUBMITTER: El-Sayes N 

PROVIDER: S-EPMC8971726 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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IFNAR blockade synergizes with oncolytic VSV to prevent virus-mediated PD-L1 expression and promote antitumor T cell activity.

El-Sayes Nader N   Walsh Scott S   Vito Alyssa A   Reihani Amir A   Ask Kjetil K   Wan Yonghong Y   Mossman Karen K  

Molecular therapy oncolytics 20220316


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  ...[more]

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