# Combination of oncolytic viruses and immune checkpoint inhibitors for treatment of high-grade gliomas

## TL;DR

Combining oncolytic viruses with immune checkpoint inhibitors may improve treatment outcomes for aggressive brain cancers like glioblastoma.

## Contribution

The paper proposes combining oncolytic virotherapy with checkpoint inhibitors to overcome the immunosuppressive tumor environment in high-grade gliomas.

## Key findings

- Oncolytic viruses show preclinical efficacy in high-grade glioma models but limited clinical success alone.
- Virotherapy increases tumor infiltrating lymphocytes and immune checkpoint expression, supporting combination with immunotherapy.
- Preliminary evidence suggests that combining oncolytic viruses with checkpoint inhibitors may enhance treatment efficacy.

## Abstract

High-grade gliomas (HGG) such as glioblastoma are the most aggressive primary malignancies of the central nervous system. The median overall survival of glioblastoma is <15 months despite treatment with surgery, radiotherapy, and chemotherapy, stressing the need for additional therapeutics. Immunotherapy such as checkpoint blockade is ineffective in HGG patients owing to an immunosuppressive tumor microenvironment. Oncolytic viruses that preferentially infect and kill cancer cells represent another novel therapeutic approach and are under development for HGG treatment. We reviewed the efficacy of oncolytic viruses in HGG treatment in preclinical and clinical studies and gathered evidence suggesting the feasibility and advantage of combining oncolytic virotherapy with checkpoint blockade. We found that significant therapeutic effects of various oncolytic viruses have been validated in preclinical HGG models, but the clinical efficacy of oncolytic virotherapy alone is limited. Accumulation of tumor infiltrating lymphocytes and upregulation of immune checkpoints within tumor microenvironment following virotherapy justify the use of checkpoint inhibitors in combination with oncolytic viruses. Preliminary results indicate this combination may yield enhanced efficacy in HGG treatment. These findings suggest that oncolytic viruses combined with immunotherapy such as checkpoint blockade may have superior efficacy compared with virotherapy alone. Future studies should further assess this hypothesis using different combinations of oncolytic viruses and checkpoint inhibitors. Combined oncolytic virotherapy and immunotherapy may become an effective treatment modality to improve the survival of HGG patients.