LILRB3

Leukocyte immunoglobulin-like receptor B3 (LILRB3) is an inhibitory receptor predominantly expressed on myeloid cells, where it regulates immune suppressive functions through tyrosine-based inhibitory motifs (ITIM)^[1][2]. Mechanistically, LILRB3 activation modulates the activity of immunosuppressive myeloid cells, including myeloid-derived suppressor cells (MDSCs), thereby facilitating tumor development in solid cancers^[1]. In acute myeloid leukemia (AML), LILRB3 engages the TRAF2-cFLIP-NF-κB signaling axis to enhance leukemic cell survival and inhibit T-cell-mediated anti-tumor responses^[3]. Compared with related isoforms LILRB1 and LILRB2, LILRB3 is specifically expressed on myeloid populations and exhibits distinct ligand interactions, including activation by galectin-4, galectin-7, and APOE4, which drive context-dependent immune modulation^[1][4]. Targeting LILRB3 with antagonistic antibodies or CAR T-cell therapy suppresses leukemia progression, upregulates myeloid differentiation factors such as PU.1 and C/EBP, and reduces proliferation regulators including AKT and cyclin D1^[5]. Agonistic ligation of LILRB3 on primary monocytes induces potent immunosuppressive effects, including decreased T-cell proliferation and enhanced engraftment tolerance in humanized models, demonstrating its utility as a myeloid checkpoint in experimental applications^[2]. These properties underscore LILRB3 as a critical myeloid-restricted inhibitory receptor with potential therapeutic relevance in cancer immunotherapy and AML-specific interventions^[1][5][2].