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

The CD47-SIRPα axis is a critical innate immune checkpoint that regulates the phagocytic activity of myeloid cells, such as macrophages and dendritic cells [1, 3, 5]. CD47, also known as leukocyte surface antigen CD47 or integrin-associated protein (IAP), is a ubiquitously expressed transmembrane protein that serves as a "don't eat me" signal by binding to Signal-regulatory protein alpha (SIRPα) on the surface of phagocytes [3, 8, 9, 11]. This interaction triggers inhibitory signaling through SIRPα's cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which prevents the engulfment of healthy cells [8, 22]. Many cancers exploit this pathway by overexpressing CD47 to evade immune surveillance, a mechanism that is often associated with poor clinical prognosis in both hematologic and solid tumors [6, 7, 12]. Therapeutic strategies targeting this axis, including monoclonal antibodies and SIRPα-Fc fusion proteins, aim to block the CD47-SIRPα interaction to restore macrophage-mediated phagocytosis and potentially enhance adaptive T-cell responses [3, 13, 21]. However, the ubiquitous expression of CD47 on normal cells, particularly red blood cells and platelets, presents significant safety challenges such as treatment-induced anemia and thrombocytopenia [4, 10, 12].

Other names

Integrin-associated proteinIAPOA3MER6Signal-regulatory protein alphaSIRPαCD172aSHPS-1BITP84Leukocyte surface antigen CD47CD47-SIRPα signaling pathway

Blockade of the CD47-SIRPα interaction to restore macrophage-mediated phagocytosis of target cells.