Logtenberg et al. thoroughly review the signaling between the SIRPα receptor (found on myeloid cells) and its ligand CD47 (the “don’t eat me” signal found on many types of healthy and cancer cells). The CD47-SIRPα axis regulates tissue homeostasis and plays a role in fibrotic diseases, atherosclerosis, and cancer. While blockade of the CD47-SIRPα axis alone has been ineffective in tumors, it has significantly enhanced the antitumor response in immunotherapy combinations. A key unanswered question for targeting the CD47-SIRPα axis is understanding the dynamic and spatial balancing of inhibitory signaling with activating signals.
Contributed by Anna Scherer
ABSTRACT: The cytotoxic activity of myeloid cells is regulated by a balance of signals that are transmitted through inhibitory and activating receptors. The Cluster of Differentiation 47 (CD47) protein, expressed on both healthy and cancer cells, plays a pivotal role in this balance by delivering a “don’t eat me signal” upon binding to the Signal-regulatory protein alpha (SIRPα) receptor on myeloid cells. Here, we review the current understanding of the role of the CD47-SIRPα axis in physiological tissue homeostasis and as a promising therapeutic target in, among others, oncology, fibrotic diseases, atherosclerosis, and stem cell therapies. We discuss gaps in understanding and highlight where additional insight will be beneficial to allow optimal exploitation of this myeloid cell checkpoint as a target in human disease.