Fig. 1

Mechanism of immunogenic cell death induction via oncolytic viruses and priming of anti-tumor specific responses mediated by antigen presenting cells. Oncolytic viruses (OVs) attack and destroy tumor cells preferentially. Lysis of tumor cells releases TAAs and PAMPs which trigger PRRs, which then produce inflammatory cytokines and antiviral type I IFNs. Viruses can activate cell death pathways, resulting in immunogenic cell death phenotypes such as necroptosis, pyroptosis, immunogenic apoptosis, and autophagic cell death. Subsequently DAMPs such as ATP, HMGB1, CALR, and type I IFNs are released by ICD from dying cancer cells. Antigen-presenting cells, such as DCs, are recruited to the tumor site. P2Y2 and P2X7 are purigenic receptors that increase DC recruitment and maturation, respectively, when extracellular ATP binds to them. CALR enhances phagocytosis and the production of proinflammatory cytokines through binding to LRP1. Also, binding HMGB1 to TLR-4, promote cytokine production and cross-presentation of antigen. IFNs bind to IFNR and promote the production of a vast number of IFN-stimulated genes that help to induce adaptive immune responses. Mature DCs can present cancer-related Ags to cancer-specific T cells, resulting in anti-tumor immunity and cytolysis mediated by perforin and granzyme B. HMGB1 High mobility group box 1, ATP adenosine triphosphate, type-I IFN type-I interferon, CALR calreticulin, PRR Pattern Recognition Receptor, TLR4 Toll-like receptor 4, LRP1 low density lipoprotein receptor–related protein 1, IFNAR interferon-α/β receptor, DAMPs Damage-associated molecular patterns, ICD Immunogenic cell death, TAAs tumor-associated antigens, PAMPs Pathogen-Associated Molecular Pattern, DCs Dendritic cells