Figure 2.

Mechanism of action of VSV therapy. (A) The intervention of monoclonal IFNAR antibody blocks the VSV-mediated IFN inflammatory pathway and reduces type I IFN-induced PD-L1 expression. Its low expression reduced PD-L1 binding to T cells, which thus exerted normal antitumor effects. (B) VSV strongly induced the JAK/STAT pathway, and inhibition of JAK/STAT using lusolidin prevented IFN-mediated antiviral response to VSV immune clearance, which promoted VSV replication and dissemination. Similarly, type I IFN-induced PD-L1 expression was reduced, thus preventing PD-L1 from binding to T cells and providing conditions for T cells to exert normal anti-tumor effects. (C) APOBEC3 gene expression is mediated by type I IFN, targeted inhibition of APOBEC3 gene can reduce IFN-mediated tumor resistance. (D) SFN through Nrf2/HO-1 pathway activates autophagy to inhibit IRF3 activity, which suppresses the type I IFN response. The inhibition of IFN response reduces the restriction of replication of VSVΔ51, so VSV exerts its normal oncolytic effect.