CD47–Signal regulatory protein alpha axis (CD47/SIRPα)

CD47 is a ubiquitously expressed, atypical immunoglobulin superfamily receptor with five transmembrane domains, functioning as a cell-surface "self" marker that inhibits phagocytosis through interaction with its inhibitory receptor SIRPα on myeloid lineage cells such as macrophages and dendritic cells. The ligation of CD47 to SIRPα transduces a negative signal via immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in the SIRPα cytoplasmic tail, recruiting SHP1/2 phosphatases and downstream inhibition of phagocytic pathways. This pathway acts as an innate immune checkpoint, analogous to T cell checkpoint pathways, and is exploited by tumor cells to evade immune clearance. The CD47/SIRPα axis is a validated and intensively pursued therapeutic target in oncology, with blockade strategies showing promise to enhance anti-tumor immunity. However, the ubiquitous expression of CD47, including on erythrocytes, introduces significant safety challenges in clinical development[1][2][3][4][5][6][7][8].

Other names

Integrin-associated proteinIAPOA3CD172aSHPS-1

Blockade of CD47/SIRPα interaction ("don't-eat-me" signal inhibition); Promotion of macrophage-mediated phagocytosis of target cells; Activation of innate immune clearance by disrupting inhibitory checkpoint; Some agents act as decoy receptors, some as antagonistic antibodies.