Signal-regulatory protein alpha and Signal-regulatory protein beta-1 (SIRPα/SIRPβ1)

Signal-regulatory protein alpha (SIRPα) and Signal-regulatory protein beta-1 (SIRPβ1) are key members of the SIRP family of membrane glycoproteins, predominantly expressed on myeloid cells like macrophages, neutrophils, and dendritic cells [5, 8, 17]. SIRPα serves as an inhibitory receptor that recognizes CD47, a "don't eat me" signal widely expressed on healthy cells and often overexpressed on cancer cells to evade immune destruction [2, 4, 10]. Upon binding CD47, SIRPα recruits phosphatases like SHP-1 and SHP-2 to inhibit phagocytosis [8, 14, 16]. Conversely, SIRPβ1 is an activating receptor that lacks an inhibitory cytoplasmic tail and instead signals through the ITAM-containing adaptor protein DAP12 to stimulate immune cell functions [1, 11, 16]. In oncology, the SIRPα/SIRPβ1 axis is targeted to disrupt the immunosuppressive signals in the tumor microenvironment and promote the clearance of malignant cells by the innate immune system [2, 6, 7]. Drugs targeting these receptors, such as monoclonal antibodies and bispecifics, are being developed to enhance anti-tumor efficacy while minimizing the hematologic toxicities typically seen with direct CD47-targeting agents [3, 15, 21].

Other names

CD172aCD172bSHPS-1BITMFRMYD-1P84PTPNS1SIRP-alphaSIRP-beta-1

Blockade of the CD47-SIRPα inhibitory interaction to enhance macrophage phagocytosis and neutrophil-mediated tumor cell killing; modulation of SIRPβ1 to promote activating signals in myeloid cells.