The CD47–SIRPα pathway in cancer immune evasion and potential therapeutic implications

Multiple lines of investigation have demonstrated that the immune system plays an important role in preventing tumor initiation and controlling tumor growth. Accordingly, many cancers have evolved diverse mechanisms to evade such monitoring. While multiple immune cell types mediate tumor surveillance, recent evidence demonstrates that macrophages, and other phagocytic cells, play a key role in regulating tumor growth through phagocytic clearance. In this review we highlight the role of tumor immune evasion through the inhibition of phagocytosis, specifically through the CD47–signal-regulatory protein-α pathway, and discuss how targeting this pathway might lead to more effective cancer immunotherapies.

► Phagocytic cells, macrophages, regulate tumor growth through phagocytic clearance.
► CD47 binds SIRPα on phagocytes which delivers an inhibitory signal for phagocytosis.
► A blocking anti-CD47 antibody enabled phagocytic clearance of many human cancers.
► Phagocytosis depends on a balance of anti-(CD47) and pro-(calreticulin) signals.
► Anti-CD47 antibody synergized with an FcR-engaging antibody, such as rituximab.