Cellular Factors Promoting Resistance to Effective Treatment of Glioma with Oncolytic Myxoma Virus

摘要: Oncolytic virus therapy is being evaluated in clinical trials for human glioma. While it widely assumed that the patient's immune response to infection limits therapy's utility, investigations into specific cell type(s) involved this have been performed using non-specific pharmacological inhibitors or allogeneic models with compromised immunity. To identify cells participate clearing an oncolytic glioma, we used flow cytometry and immunohistochemistry immunophenotype orthotopic glioma model immunocompetent mice after Myxoma (MYXV) administration. These studies revealed a large resident microglia macrophage population untreated tumours, robust monocyte, T NK infiltration 3 days following MYXV infection. determine role on utility of combination knockout mouse strains immunocyte ablation techniques. Collectively, our experiments important tumour-resident myeloid overlapping roles recruited clearance efficacy from gliomas. Using cyclophosphamide regimen achieve lymphoablation prior during treatment, prevented treatment-induced peripheral recruitment and, surprisingly, largely ablated population. Virotherapy CPA-treated animals resulted sustained viral within as well substantial survival advantage. This study demonstrates resistance virotherapy syngeneic involves multi-faceted cellular can be overcome CPA-mediated lymphoablation.