Figure 1.

Induction of immune conversion of tumor microenvironment by OVs. The left panel depicts a cold tumor microenvironment (TME). In addition to tumor cells, some other components of the TME are shown, i.e., blood vessel with endothelial cells, CAFs, ECM, and few infiltrating immune cells. These immune cells (mainly Treg, MDSC, and TAM having a M2 immunosuppressive status), together with other cells of TME (e.g., CAF and tumor cells themselves), produce and secrete chemo/cytokines, growth factors, and other molecules which contribute to create an immunosuppressive TME. This “cold” TME supports tumor development and metastasis, and confers resistance to (immuno) therapies. The right panel depicts an inflamed TME after intravenous OV treatment. OVs reach the tumor through the blood stream and act in a multimodal fashion to eliminate cancer cells. OVs specifically replicate in and kill cancer cells by inducing immunogenic cell death. Virus-induced cancer cell lysis is associated with the release of progeny virus particles, TAAs, DAMPs, PAMPs, and pro-inflammatory/immunostimulatory cytokines which contribute to recruiting immune cells in the TME and inducing maturation of DCs, thereby triggering innate as well as adaptive immune responses (inset a). DCs migrate to the draining lymph nodes where they cross-present TAAs to T cells (inset b). After expansion, T cells infiltrate the TME and participate in the destruction of cancer cells together with other effector cells such as NK cells and M1-converted macrophages (inset c). Some OVs may also infect endothelial cells and induce disruption of tumor vasculature, potentially facilitating immune cell migration into the TME (inset d).