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

The CD47–Signal regulatory protein alpha (SIRPα) interaction interface is a critical innate immune checkpoint that regulates the "don't eat me" signaling pathway between target cells and myeloid cells, such as macrophages (UniProt: P78324, P50851). CD47 is a ubiquitously expressed transmembrane protein that, upon binding to the N-terminal V-set domain of SIRPα on macrophages, triggers the recruitment of SHP-1 and SHP-2 phosphatases to inhibit pro-phagocytic signals (PubMed: 32103353). Many cancer types overexpress CD47 to evade immune surveillance, making this interface a significant target for therapeutic intervention in oncology (PubMed: 33434177). Drugs targeting this axis, including monoclonal antibodies like magrolimab and decoy receptors like evorpacept, aim to disrupt this binding to restore the ability of the innate immune system to clear malignant cells. However, the widespread expression of CD47 on healthy tissues, particularly red blood cells, presents significant clinical challenges, including treatment-induced anemia and hemagglutination (PubMed: 31110040). Beyond oncology, this interaction is also being investigated for its role in cardiovascular diseases like atherosclerosis and various inflammatory conditions.

Other names

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

Blockade of the interaction between CD47 on target cells and SIRPα on myeloid cells, thereby neutralizing the inhibitory "don't eat me" signal and promoting macrophage-mediated phagocytosis of diseased cells.