CD47–Signal regulatory protein alpha protein-protein interface (CD47–SIRPα interface)

The CD47–Signal regulatory protein alpha (SIRPα) protein-protein interface represents an immune checkpoint pathway in which CD47, expressed on most cell types—especially at high levels on tumors—binds to inhibitory SIRPα receptors present on myeloid cells such as macrophages and dendritic cells. This interaction transmits an inhibitory signal that prevents the innate immune system from engulfing and destroying cells, functioning as a "don't-eat-me" signal. Tumor cells exploit this interface to evade immune surveillance. Therapeutic blockade of this interface, using antibodies or fusion proteins, removes the inhibition and enables immune cells to attack tumor cells more efficiently, making it a major target in cancer immunotherapy. The pathway also plays roles in immune homeostasis, inflammation, neuronal function, and possibly autoimmunity. Safety concerns arise due to the broad expression of CD47 on healthy tissues, requiring carefully engineered therapeutics to minimize off-target effects.

Other names

CD47–SIRPα axisCD47–SIRPα checkpointCD47–SHPS-1 interactionCD47–CD172a interaction

Blockade of CD47–SIRPα interaction removes the "don't-eat-me" signal, allowing macrophages to phagocytose tumor cells. Augmentation of antibody-dependent cellular cytotoxicity (ADCC) against cancer cells by overcoming inhibitory signaling.