LILRB2

Leukocyte immunoglobulin-like receptor B2 (LILRB2) functions as an inhibitory immune receptor primarily expressed on myeloid cells, modulating immune responses via binding to HLA class I molecules^[1][2]. Mechanistically, LILRB2 engages SHP2 and downstream CaMK1/CREB signaling pathways to regulate proliferation, migration, and differentiation of target cells^[1]. In disease models, LILRB2 contributes to immune evasion in cancers and infectious diseases, including endometrial cancer progression and Plasmodium falciparum infection through interaction with RIFIN ligands^[1][3]. Compared with related isoforms LILRB1 and LILRB4, LILRB2 exhibits distinct ligand specificity, particularly recognizing domain 3 of RIFIN and classical HLA molecules, conferring unique inhibitory functions in immune surveillance^[3][4]. Overexpression of LILRB2 in experimental myopia reduced scleral remodeling and intraocular inflammation by modulating the MEK-ERK-P65 axis and macrophage polarization, highlighting its functional versatility in non-cancer models^[5]. Pharmacologically, selective antagonists such as OR502 and dual LILRB1/2 blockers (OR641) have demonstrated the ability to reverse myeloid cell-mediated immunosuppression, enhance T cell effector responses, and promote Th1-like immune activity in preclinical and early-phase clinical studies^[6][7]. These agents facilitate experimental modulation of the tumor microenvironment and may serve as tools for mechanistic investigations of LILRB2 in immunotherapy and disease modeling^[6][7].