Cluster of differentiation 47 (CD47) (CD47)

Cluster of differentiation 47 (CD47), often referred to as the prototype 'macrophage immune checkpoint,' is a transmembrane protein that functions as a critical 'don't eat me' signal to the innate immune system. It is widely overexpressed on the surface of various cancer cells, including myeloid leukemias and solid tumors, to evade phagocytic clearance by macrophages. CD47 exerts its inhibitory effect by binding to Signal Regulatory Protein Alpha (SIRPα) on macrophages, triggering a signaling cascade that prevents the accumulation of myosin at the phagocytic synapse. In the context of oncology, therapeutic strategies focus on blocking the CD47-SIRPα axis using monoclonal antibodies or decoy receptors to restore the ability of macrophages to identify and eliminate malignant cells. While highly promising, targeting CD47 presents significant clinical challenges, most notably on-target anemia caused by the high expression of CD47 on aged erythrocytes, necessitating specialized dosing regimens or engineered molecules to spare healthy blood cells.

Other names

Integrin-associated proteinIAPMER6OA3Don't eat me signal

CD47 acts as a 'don't eat me' signal by binding to SIRPα on macrophages, which inhibits phagocytosis. Therapeutic antibodies block this interaction, enabling macrophages to engulf and destroy cancer cells.