CD47/SIRPα (SIRPa) interaction

Class

CD47/SIRPα blocking agent (myeloid immune checkpoint inhibitor)

Pathway

Restores macrophage-mediated phagocytosis of tumor cells

CD47 is a protein expressed on the surface of most cells in the body, including many cancer cells, where it is often found at unusually high levels. It functions as a signal that tells macrophages, immune cells that engulf and destroy abnormal or damaged cells, to leave a cell alone. CD47 does this by binding to a receptor called SIRPα (signal regulatory protein alpha) on the macrophage surface. Tumors exploit this interaction to evade destruction, effectively camouflaging themselves from the innate immune system. Blocking the CD47/SIRPα interaction, using antibodies or engineered proteins directed at either partner, removes this inhibitory signal and allows macrophages to recognize and phagocytose (engulf) tumor cells more readily, particularly when the cells also display markers that flag them for removal, such as antibody coatings or other 'eat-me' signals. This mechanism is broadly relevant across many cancer types because CD47 overexpression is common, and it represents a distinct immunotherapy strategy from T-cell checkpoint inhibition, instead engaging the innate immune system's phagocytic cells. It is often explored in combination with other anticancer approaches that increase the visibility of tumor cells to macrophages.