Signal regulatory protein alpha (SIRPα) variant 1 (SIRPαV1)

Signal regulatory protein alpha (SIRPα) is a transmembrane inhibitory receptor primarily expressed on myeloid cells, including macrophages and dendritic cells (UniProt P78324). It plays a pivotal role in immune homeostasis by binding to CD47, a ligand expressed on healthy cells that transmits a don't eat me signal to inhibit phagocytosis (Nature Reviews Cancer, 2020). SIRPα is highly polymorphic in humans, with variant 1 (V1) being one of the two most prevalent alleles; these variants differ in their extracellular IgV domain, which can influence binding kinetics and therapeutic targeting (PubMed: 25605871). In many malignancies, the CD47-SIRPα axis is exploited by tumor cells to evade the innate immune system, making it a high-priority target in immuno-oncology. Therapeutic strategies targeting SIRPαV1 include monoclonal antibodies and SIRPα-Fc fusion proteins, which aim to disrupt the inhibitory signal and enhance the anti-tumor activity of macrophages. By specifically targeting SIRPα rather than the ubiquitously expressed CD47, these therapies potentially avoid the hematologic toxicities, such as anemia, often associated with CD47-blocking agents.

Other names

CD172aSHPS-1PTPNS1BITMFRSignal-regulatory protein alpha-1SIRP alpha variant 1

Antagonizing the interaction between SIRPα and CD47 to block the inhibitory don't eat me signal, thereby promoting macrophage-mediated phagocytosis of tumor cells (Nature Reviews Drug Discovery, 2019).