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

The CD47–SIRPα interaction interface serves as a critical 'don't eat me' signal that regulates the phagocytic activity of the innate immune system. CD47 is a transmembrane protein widely expressed on the surface of many cell types, while SIRPα is an inhibitory receptor primarily found on myeloid cells such as macrophages and dendritic cells (UniProt P61273, P78324). When CD47 binds to SIRPα, it triggers a signaling cascade involving the recruitment of SHP-1 and SHP-2 phosphatases, which inhibits pro-phagocytic signals and prevents the clearance of healthy cells (Matlung et al., 2017). Many cancer cells overexpress CD47 to evade immune surveillance and avoid being engulfed by macrophages, making this interface a high-priority target in oncology (Chao et al., 2012). Therapeutic strategies targeting this axis, including monoclonal antibodies like Magrolimab and decoy receptors like Evorpacept, aim to disrupt this interaction to restore the immune system's ability to eliminate malignant cells (Sallman et al., 2023). However, because CD47 is also expressed on red blood cells, therapeutic blockade can lead to significant safety concerns such as treatment-induced anemia and hemagglutination (Pietsch et al., 2017).

Other names

CD47-SIRPα axisDon't eat me signalIntegrin-associated protein-SIRPα interactionCD47-CD172a interactionIAP-SIRPα interaction

Blockade of the inhibitory CD47–SIRPα interaction to promote macrophage-mediated phagocytosis of target cells.