Figure 1.

Proposed model for ICD and pro-inflammatory cytokines/chemokines (Th1) promotion of oncolytic virus (OV)-mediated antitumor-immunity. (1) OV infects tumor cells and induces ICD, leading to the release/presentation of signal 0 [damage-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs)], along with tumor-associated antigens (TAAs) to dendritic cells (DCs), resulting in DC activation and Ag cross-presentation to antiviral and antitumor immune cells (activated NK cells, CD4⁺ and CD8⁺ T cells), followed by clonal expansion and maturation of antitumor T effector cells. (2) Cytokines/chemokines released during the acute inflammation in the tumor microenvironment (TME) promote trafficking of therapy-induced immune cells into the TME; (3) inflammation in the TME is sponsored by both viral- and tumor-reactive T cells, with immune-mediated eradication of tumor cells and tumor-associated stromal cells. Additional danger signals (signal 0), inflammatory cytokines, and chemokines (signal 3) and TAAs (signal 1) further activate tumor-associated DCs, overcoming local immunosuppression and prolonging the survival and functionality of antitumor immune cell populations; (4) reiterative rounds of DC-mediated cross-priming continue to allow for delivery of new (reinforcement) T immune effector cells into the TME (5) allowing for sustained antitumor efficacy within disseminated sites of disease.