Targeting CD37 promotes phagocytosis against multi cancer cell

Macrophages play vital roles in innate and adaptive immunity, and their indispensable functions are accomplished by phagocytosis and antigen presentation. Great efforts have been made to explore the potential mechanism of action of potential phagocytosis checkpoints. However, the use of a systematic checkpoint scanning strategy is far from satisfactory. We thus established an in vitro phagocytosis assay using primary healthy donors’ macrophages and breast cancer cells. Equal numbers of cells were sorted and subjected to ribosome profiling, and immune system-specific checkpoints were ultimately identified. CD37 was dramatically downregulated in phagocytic macrophages and targeting CD37 with a specific antibody promoted phagocytosis of multiple cancer cells. Tumorous macrophage migration inhibitory factor (MIF) directly binds to CD37 and promotes the recruitment of SHP1. Targeting CD37 enhances the efficacy of CD47 in vivo and in vitro. In all, our study identified a previously unidentified phagocytosis checkpoint and provided new potential for precise therapy.