Targeting macrophage-mediated tumor cell phagocytosis: An overview of phagocytosis checkpoints blockade, nanomedicine intervention, and engineered CAR-macrophage therapy

Immunotherapy has been developing at an unprecedented speed with promising therapeutic outcomes in the wide spectrum of cancers. Up until now, most immunotherapies have focused on adaptive immunity; however, investigating the potential of macrophage phagocytosis and consequent adaptive immune cross-priming has led to a growing interest in exploiting macrophages in cancer therapy. In light of the positive evidence from preclinical studies and early clinical data, targeting macrophage phagocytosis has become a promising therapeutic strategy. Here, we review therapies based on harnessing and amplifying macrophage phagocytosis, such as blocking phagocytosis checkpoints and exploiting nanoparticles as efficient approaches in elevating macrophages-mediated phagocytosis. The present study introduces CAR-macrophage as the state-of-the-art modality serving as the bridge between the innate and adaptive immune system to mount a superior anti-tumor response in the treatment of cancer. We also take a look at the recent reports of therapies based on CAR-engineered macrophages with the hope of providing a future research direction for expanding the application of CAR-macrophage therapy.