Targeting CD37 promotes macrophage-dependent phagocytosis of multi cancer cell types and facilitates tumor clearance in preclinical mouse models

Despite efforts to identify phagocytic checkpoints and explore their mechanisms of action, current checkpoint scanning strategies are unable to provide a complete and systematic list of such immune checkpoints. Here, we use primary healthy donor macrophages co cultured with breast cancer cells for in vitro phagocytosis assay, and then carry out ribosome analysis on the sorted macrophages to identify immune system specific checkpoints.

Interestingly, we observed downregulation of CD37 in phagocytic macrophages and demonstrated that targeting CD37 with specific antibodies can promote phagocytosis of various cancer cells in vitro. Mechanistically, tumor derived macrophage migration inhibitory factor (MIF) directly binds to CD37, activating the transduction cascade involving recruitment of SHP1 and inhibition of AKT signaling, ultimately impairing phagocytosis.