Leukocyte surface antigen CD47-Signal-regulatory protein alpha interaction (CD47-SIRPα)

The CD47-Signal regulatory protein alpha (SIRPα) interaction is a critical innate immune checkpoint that functions as a "don't eat me" signal to regulate phagocytosis [1, 3]. CD47 is a ubiquitously expressed transmembrane protein that binds to SIRPα, an inhibitory receptor primarily found on macrophages and dendritic cells [2, 9]. This binding triggers a signaling cascade involving the recruitment of SHP-1 and SHP-2 phosphatases, which inhibits the pro-phagocytic activity of the myeloid cell [2, 11]. Many cancers overexpress CD47 to evade immune surveillance, making the disruption of this interaction a major therapeutic goal in oncology [2, 10]. Drugs such as monoclonal antibodies (e.g., magrolimab) and fusion proteins (e.g., evorpacept) block this axis to restore macrophage-mediated clearance of tumor cells and enhance adaptive immune responses through improved antigen presentation [1, 13]. However, the presence of CD47 on red blood cells poses a significant safety challenge, often leading to treatment-induced anemia and requiring specialized dosing strategies to mitigate toxicity [1, 5, 8].

Other names

CD47-SIRPα axisCD47-SIRPα pathwayIntegrin-associated protein-Signal-regulatory protein alpha interactionIAP-SHPS-1 interactionCD47-CD172a interaction

Blockade of the CD47-SIRPα interaction to restore macrophage-mediated phagocytosis of tumor cells and enhance antigen presentation to T cells.