FIGURE 2.

Oncolytic viruses can induce host systemic anti-tumor immunity to kill tumor cells. Following viral infection, viral replication leads to ER stress and genotoxic stress in tumor cells, which results in the release of the viral elements TAAs, PAMPs, and DAMPs. Sensing elements, such as PRRs, can recognize these molecules, which leads to immune cell activation and inflammatory signal transduction. With virus replication, antiviral pathways can be activated. This activation induces the production of cytokines and type I IFNs, which mediate the activation and maturation of immune cells, such as DCs and NK cells. NK cells migrate to the tumor area under the action of chemokines, such as IL-12, IL-2, and IFN-α/β, and exert antitumoral properties by releasing IFN-γ, TNF-α and CD107. Mature DCs can present antigenic peptides within the context of MHC I molecules to CD4⁺ T cells and within the context of MHC II molecules to CD8⁺ T cells. CD8⁺ T cells are also activated through the stimulation of CD4⁺ T cells. The activation of CD4⁺ T cells by DCs helps to activate CD8⁺ T cells by inducing the production of cytokines such as IL‐2. The recognition of tumor surface antigens by antibodies can trigger CTL killing of tumor cells through Fas-FasL interactions, TNF‐TNFR signaling, and the perforin/granzyme pathway.