Figure 1.

Mechanism of oncolytic virotherapy. When oncolytic viruses attack a normal cell, viruses activate JAK-STAT or NF-κB pathways through interaction between TLRs and PAMPs, which induce type I IFN transcription and release. Then, type I IFN activates PKR, which is essential for regulating abnormal cell proliferation and innate cellular antiviral responses. However, when oncolytic viruses attack cancer cells, interferon signaling and PKR activity are inhibited; thus, virus clearance is blocked, enabling virus replication. Following virus replication, most oncolytic viruses can induce cell death, at which time they release not only tumor-associated antigens that can promote an adaptive immune response but also viral PAMPs and additional cellular DAMPs and cytokines. These released molecules recruit antigen-presenting cells (APCs) and promote their maturation, subsequently activating antigen-specific CD4⁺ and CD8⁺ T cell responses, enabling CD8⁺ T cells to expand into cytotoxic effector cells and mediate antitumor immunity.