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Publications of the Week

Oncolytic Virotherapy Blockade by Microglia and Macrophages Requires STAT1/3

By November 28, 2017November 29th, 2017No Comments

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 This week we profile a recent publication in Cancer Research from Dr. William Jia  at the University of British Columbia.

Can you provide a brief overview of your lab’s current research focus?

My lab at UBC has been working on oncolytic virotherapy for many years and it is still my major interest. At the same time, we also work on using viral vectors for gene therapy in areas of neurological diseases

What is the significance of the findings in this publication?

Clinical tumors are highly heterogenic that contain many non-tumor cells. In the case of malignant brain tumors, a large portion of cells in the tumor are microglia. Since microglia are not tumor cells, which, by definition, cannot support oncolytic virus replication. Furthermore, we found in the present study that those microglia/macrophages are still infectable by the virus. In another word, those non-tumor cells in the tumor microenvironment allow the virus to enter but not to replicate. Therefore, those cells are actually traps for oncolytic virus to block the viral dissemination in the tumor mass. In this work, we discovered that the reason those microglia/macrophages are not permissive for oncolytic virus replication is that the levels of STAT1/3 activity in those cells are induced to high levels when they are infected. We further found a compound that inhibits STAT1/3 activity is able to allow those tumor associated microglia and macrophages to support virus replication. As a result, it significantly enhanced the efficacy of oncolytic virotherapy in our animal tumor models. Since STATs inhibition is also tumor suppressive, our findings may provide a new strategy that is potentially useful in combination with oncolytic virotherapy to treat cancer patients for a better outcome.

What are the next steps for this research?

We are now interested in knowing more details about the mechanisms of STAT1/3 inhibition in the context of oncolytic virotherapy. In addition, we found inhibiting STAT1/3 not only enhanced efficacy of virotherapy but also enhanced the safety of the virus to normal tissues. We are very interested in further investigating the reason. Finally, there are already some anti-STAT drugs in clinic for treating cancers, we are interested in testing those drugs in our models as well as moving to clinical trials in near future.

This research was funded by:

This study was partially sponsored by Canadian Cancer Society and also by Virogin Biotechnology Ltd.

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