Abstract Details
Name
Itaconate is induced by oncolytic VSV infection and limits viral replication in tumor cells
Presenter
Dominic Roy, Centre de Recherche du CHUM/Université de Montréal
Co-Author(s)
Jessica Meunier1,2, Melvina Badet1,2, Chloe Nassar1,2, Angelina Bardoul1,2, Dominic Roy1,2 1. Centre de Recherche du CHUM. 2. Université de Montréal
Abstract Category
Fighting & Responding
Abstract
Oncolytic viruses (OVs) infect and kill cancer cells while having limited toxicity in normal tissues. Despite promising clinical trial results supporting the therapeutic benefit of OVs, there are many aspects of OV therapy that remain poorly understood. One aspect of OV therapy that is not well defined is the impact of tumor metabolism. While it is appreciated that the increased metabolic activity of tumor cells supports OV replication, the role of specific metabolites and metabolic pathways in regulating OV therapy is less clear. To identify metabolic changes that occur in tumor cells following OV infection, we performed metabolic profiling and identified the metabolite itaconate as being significantly increased. Itaconate is produced by the interferon (IFN) inducible enzyme Irg1 and its production is thought to be limited mainly to immune cells such as macrophages. Our preliminary data suggests that itaconate negatively regulates the replication of the OV vesicular stomatitis virus (VSV) in tumor cells. Accordingly, inhibiting or knockout Irg1 results in increased virus replication. Ongoing studies are aimed at understanding how Irg1 and itaconate regulate antiviral immunity. Overall, our findings suggest that targeting itaconate production to may be a promising approach to improve OV therapy. The finding that itaconate is produced by tumor cells has significant implications in the context of cancer that extend beyond OV therapy and will open new avenues of research focused on understanding how itaconate contributes to the metabolic crosstalk between tumor cells and immune cells within the tumor microenvironment.
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