Leukocyte immunoglobulin-like receptor subfamily B member 2 and 4 (LILRB2 and LILRB4) (ILT4 and ILT3)

Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2/ILT4) and member 4 (LILRB4/ILT3) are inhibitory receptors primarily expressed on myeloid cells, such as macrophages, monocytes, and dendritic cells (UniProt Q8N423, Q8NHJ6). These receptors function as myeloid immune checkpoints that regulate immune tolerance by binding to various ligands, including MHC class I molecules (like HLA-G) and Apolipoprotein E (APOE) (Zhang et al., J Hematol Oncol, 2021). In the tumor microenvironment, the interaction between these receptors and their ligands promotes an immunosuppressive M2-like macrophage phenotype, which inhibits T-cell activation and facilitates tumor growth (Chen et al., Nature, 2018). Therapeutic antibodies targeting ILT3 and ILT4 are designed to block these inhibitory signals, thereby reprogramming myeloid cells into a pro-inflammatory M1-like state that enhances anti-tumor immunity (Merck, MK-4830 Pipeline, 2023). These agents are currently being evaluated in clinical trials for solid tumors and hematologic malignancies, often in combination with PD-1/PD-L1 inhibitors to overcome resistance to T-cell-focused immunotherapies (ClinicalTrials.gov NCT03564717).

Other names

LILRB2LILRB4CD85dCD85kImmunoglobulin-like transcript 4Immunoglobulin-like transcript 3LIR-2LIR-5Leukocyte immunoglobulin-like receptor subfamily B member 2Leukocyte immunoglobulin-like receptor subfamily B member 4

Antagonistic monoclonal antibodies that block the interaction between LILRB2/LILRB4 receptors on myeloid cells and their immunosuppressive ligands (such as HLA-G or APOE), thereby reversing myeloid-mediated immunosuppression and promoting anti-tumor T-cell activity (Chen et al., Nature, 2018; Zhang et al., J Hematol Oncol, 2021).