Figure 3: Mechanism of oncolytic virus immunotherapy. Oncolytic viruses infect cancer cells and induce the immunogenic cell death and release of infectious viral progeny that infect nearby cancer cells. Tumour-associated antigens and cellular DAMPs, such as CRT, HMGB1 and cellular ATP, stimulate the host antitumour immune responses. Cellular detection of viral infection and the products of oncolysis trigger the rapid activation of host antiviral responses and influx of immune cells that mediate the destruction of residual infected and uninfected tumour cells. The direct recognition and killing of tumour cells is primarily mediated by natural killer cells of the innate immune system and tumour antigen-specific CD8+ cytotoxic and CD4+ helper T lymphocytes of the adaptive immune system. The effects of OVs reflect on MDSCs, TAMs and Treg cells inhibition and modify the suppressive microenvironment altering the cytokine milieu (red lines) OVs: oncolytic viruses; ATP: adenosine triphosphate; HMGB1: high mobility Group Box 1; CRT: calreticulin; DAMPs: damage-associated molecular pathways; CD: cluster differentiation; TLR4: Toll-like receptor 4; P2RX7: Purin 2 Receptor X7; DC: dendritic cell; MCH I: major histocompatibility complex Class I; Treg: T regulatory; TAMs: tumour-associated microenvironment; MDSCs: myeloid-derived suppressor cells. The figure was modified from Servier Medical Art, http://smart.servier.com/.