The CD47-SIRPα axis is a promising target for cancer immunotherapies

Cluster of differentiation 47(CD47) is a transmembrane protein that is ubiquitously found on the surface of many cells in the body and uniquely overexpressed by both solid and hematologic malignant cells. CD47 interacts with signal-regulatory protein α (SIRPα), to trigger a "don't eat me" signal and thereby achieve cancer immune escape by inhibiting macrophage-mediated phagocytosis. Thus, blocking the CD47-SIRPα phagocytosis checkpoint, for release of the innate immune system, is a current research focus. Indeed, targeting the CD47-SIRPα axis as a cancer immunotherapy has shown promising efficacies in pre-clinical outcomes. Here, we first reviewed the origin, structure, and function of the CD47-SIRPα axis. Then, we reviewed its role as a target for cancer immunotherapies, as well as the factors regulating CD47-SIRPα axis-based immunotherapies. We specifically focused on the mechanism and progress of CD47-SIRPα axis-based immunotherapies and their combination with other treatment strategies. Finally, we discussed the challenges and directions for future research and identified potential CD47-SIRPα axis-based therapies that are suitable for clinical application.