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

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.