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

The CD47–Signal regulatory protein alpha (SIRPα) protein–protein interface is a critical innate immune checkpoint that regulates the phagocytic activity of myeloid cells, particularly macrophages (UniProt P61273, P78324). CD47, a transmembrane protein known as the "don't eat me" signal, is expressed on the surface of most normal cells to prevent their destruction by the immune system. When CD47 binds to SIRPα on macrophages, it initiates an inhibitory signaling pathway that prevents phagocytosis (Chao et al., 2012). Many cancer types exploit this mechanism by overexpressing CD47, allowing them to evade immune surveillance and clearance (Logtenberg et al., 2020). Therapeutic agents targeting this interface, such as monoclonal antibodies and SIRPα-Fc fusion proteins, aim to block this interaction and restore the ability of macrophages to engulf and destroy malignant cells (Advani et al., 2018). However, the ubiquitous expression of CD47 on healthy cells, especially red blood cells, presents a significant clinical challenge, often resulting in treatment-related anemia and hemagglutination (Zhang et al., 2020).

Other names

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

Blockade of the CD47-SIRPα interaction to neutralize the inhibitory 'don't eat me' signal, thereby promoting macrophage-mediated phagocytosis of tumor cells.