Immunological effects of oncolytic virotherapy in the context of a preclinical model of melanoma

Conventional therapies have demonstrated little to no extension in overall survival in the context of metastatic melanomas. As a result there is growing interest in the use of novel immunotherapies. Oncolytic viruses (OVs) that are genetically engineered to express tumour antigens offer the unique combination of direct oncolytic activity and induction of tumour-specific immune responses. Interactions between OVs and the immune system are complex and further complicated by the immunosuppressive tumour microenvironment. We identified mechanisms that allow OVs to mediate their oncolytic effects, despite pre-existing immunity against a virus-encoded transgene, investigated how OVs modulate the immunological landscape within a tumour, as well as the effects of metformin supplementation on melanogenesis and the immunogenicity of melanoma cells. The goal of this thesis is to explore the interactions between the tumour, immune system and OVs in a pre-clinical model of melanoma, ultimately to support the development of effective cancer biotherapies.