Fig. 2

Oncolytic viruses can exploit cancer immune evasion pathways. The therapeutic effectiveness of oncolytic viruses arises from both direct lysis of cancer cells and the indirect activation of antitumor immune responses. Upon infection with oncolytic viruses, cancer cells trigger an antiviral response characterized by endoplasmic reticulum (ER) and genotoxic stress. This response results in the increased production of reactive oxygen species (ROS) and antiviral cytokines. ROS and cytokines, particularly type I interferons (IFNs), are released from the infected cancer cells, thereby activating immune cells such as antigen-presenting cells, CD8⁺ T cells, and natural killer (NK) cells. Oncolytic viruses then induce oncolysis, releasing viral progeny, pathogen-associated molecular patterns (PAMPs), danger-associated molecular patterns (DAMPs), and tumor-associated antigens (TAAs), including neoantigens. The release of viral progeny facilitates further infection by oncolytic viruses. PAMPs (comprising viral particles) and DAMPs (comprising host cell proteins) activate the immune system by engaging receptors like Toll-like receptors (TLRs). In this immunostimulatory environment, TAAs and neoantigens are released and captured by antigen-presenting cells. These processes collectively generate immune responses against virus-infected cancer cells and initiate new immune responses against TAAs/neoantigens on uninfected cancer cells. CD40L, CD40 ligand;