Signal regulatory protein alpha (SIRPα)-Cluster of differentiation 47 (CD47) interaction (SIRPα-CD47)

The Signal regulatory protein alpha (SIRPα)-Cluster of differentiation 47 (CD47) interaction is a critical myeloid immune checkpoint that regulates the phagocytic activity of macrophages [UniProt P78324, Q08722]. CD47 is a ubiquitously expressed transmembrane protein that serves as a "self" marker; when it binds to SIRPα on the surface of myeloid cells like macrophages and dendritic cells, it initiates an inhibitory signaling cascade through SHP-1 and SHP-2 phosphatases [Matlung et al., 2017]. This signaling effectively delivers a "don't eat me" signal, preventing the phagocytosis of healthy host cells. Many types of cancer cells exploit this pathway by overexpressing CD47, allowing them to evade immune surveillance and destruction by the innate immune system [Chao et al., 2012]. Therapeutic interventions targeting this axis, such as monoclonal antibodies against CD47 or SIRPα and decoy receptors like SIRPα-Fc fusion proteins, aim to disrupt this interaction to restore and enhance macrophage-mediated programmed cell phagocytosis of tumor cells [Logtenberg et al., 2020]. While promising, these therapies face significant safety challenges, most notably treatment-induced anemia and thrombocytopenia, because CD47 is also expressed on aged red blood cells and platelets [Zeidan et al., 2020].

Other names

CD47-SIRPα axisDon't eat me signalSHPS-1-CD47 interactionBIT-CD47 interactionCD172a-CD47 interactionIAP-SIRPα interaction

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