Fig. 4

Basic macrophage strategies in oncolytic virotherapy. Currently, there are two major directions of basic strategies for targeting the macrophage to optimize therapeutic response. On the one hand, armed OVs enhance the anti-tumor effect of macrophages. A Repolarization to an antitumor phenotype. Given the pro-tumorigenic role of M2-like tumor-associated macrophages (TAMs), the expression of pro-inflammatory cytokines or chemokines by genetically modified viruses was used to increase macrophage activity and promote the polarization of M2-like macrophages to M1-like macrophages. B Enhancement of phagocytosis by macrophages. The expression of anti-CD47 antibody or SIRPα-Fc fusion protein after viral genetic modification can disrupt “don't eat me” signaling and enhance the killing of tumor cells by macrophages. On the other hand, weakening the clearance of OVs by macrophages contributes to higher viral titers at tumor sites. C Direct macrophage depletion. Since OVs are subject to phagocytosis by macrophages and/or clearance by antiviral cytokines after delivery, brief administration of macrophage depletion agents prior to OVs treatment can cause apoptosis of macrophages, increase the titer of OVs, and change the phenotype of TAMs. D Delivered through the carrier. In addition, the use of tumorophilic carrier cells or liposomes to deliver OVs, is also able to avoid the negative effects of neutralizing antibodies and/or innate immune cells and overcome the challenges of systemic administration of OVs