Signal regulatory protein alpha–Cluster of differentiation 47 interface (SIRPα–CD47 interface)

The SIRPα–CD47 interface is a critical innate immune checkpoint that regulates the phagocytic activity of myeloid cells, particularly macrophages and dendritic cells [4, 15]. CD47, often referred to as the 'don't eat me' signal, is a ubiquitously expressed transmembrane protein that binds to the inhibitory receptor SIRPα on phagocytes, triggering a signaling cascade that prevents the engulfment of healthy 'self' cells [2, 6]. Many cancer cells exploit this pathway by overexpressing CD47 to evade immune surveillance and destruction [9, 10]. Therapeutic strategies targeting this interface aim to disrupt the inhibitory signal, thereby unmasking pro-phagocytic 'eat me' signals like calreticulin and promoting the clearance of malignant cells [5, 12]. While clinical trials have shown promise, particularly in hematologic malignancies like AML and MDS, the ubiquitous expression of CD47 on red blood cells and platelets presents significant safety challenges, including treatment-induced anemia and thrombocytopenia [1, 18]. Modern drug development focuses on 'RBC-sparing' antibodies, fusion proteins with high affinity for tumor-expressed CD47, and priming dose regimens to mitigate these hematologic toxicities [11, 14].

Other names

CD47-SIRPα axisDon't eat me signalMyeloid checkpointCD47-SIRPα signaling systemIntegrin-associated protein–Signal regulatory protein alpha interface

Blockade of the inhibitory SIRPα–CD47 interaction to restore macrophage-mediated phagocytosis of target cells, often in combination with opsonizing antibodies to provide a pro-phagocytic 'eat me' signal [1, 3, 10].