Leukocyte immunoglobulin-like receptor subfamily B (LILRB) (LILRB)

The Leukocyte Immunoglobulin-Like Receptor subfamily B (LILRB) is a group of five inhibitory receptors (LILRB1 to LILRB5) primarily expressed on myeloid lineage cells, including macrophages, monocytes, and dendritic cells (NIH, Frontiers in Immunology). These receptors function as immune checkpoints by transmitting inhibitory signals through intracellular immunoreceptor tyrosine-based inhibitory motifs (ITIMs), which recruit phosphatases such as SHP-1 and SHP-2 to dampen immune cell activation (Nature Immunology, Journal of Clinical Investigation). In many cancers, LILRBs are upregulated on tumor-associated macrophages (TAMs), where they promote an immunosuppressive M2-like phenotype and facilitate tumor evasion from immune surveillance (MDPI, Therapeuticanostics). Therapeutic intervention typically involves antagonistic monoclonal antibodies designed to block the interaction between LILRBs and their ligands, such as MHC class I or HLA-G, thereby restoring the pro-inflammatory and phagocytic activity of macrophages (PubMed, Clinical Cancer Research). Several candidates, including MK-4830 (targeting LILRB2) and IO-202 (targeting LILRB4), are currently in clinical trials for solid tumors and acute myeloid leukemia, often in combination with other checkpoint inhibitors to enhance anti-tumor efficacy (JCI, PatSnap).

Other names

Immunoglobulin-like transcript (ILT)Leukocyte inhibitory receptor (LIR)CD85CD85j (LILRB1)CD85d (LILRB2)CD85a (LILRB3)CD85k (LILRB4)CD85c (LILRB5)ILT2ILT3ILT4ILT5LIR-1LIR-2LIR-3LIR-5LIR-8

Antagonistic monoclonal antibodies block the interaction between LILRB receptors and their ligands (e.g., MHC-I, HLA-G, APOE), preventing inhibitory signaling via ITIM motifs and SHP-1/2 phosphatases. This blockade relieves the suppression of myeloid cells, particularly macrophages, promoting their polarization from an immunosuppressive M2-like phenotype to a pro-inflammatory M1-like phenotype and enhancing anti-tumor immune responses.