Leukocyte immunoglobulin-like receptor subfamily B member 1 and Leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB1/LILRB2)

Leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1/ILT2) and member 2 (LILRB2/ILT4) are key inhibitory receptors expressed on various immune cells, including myeloid cells, natural killer (NK) cells, and T cells [UniProt, PubMed]. These receptors function as immune checkpoints by binding to major histocompatibility complex (MHC) class I molecules, particularly the non-classical HLA-G, which is frequently overexpressed in tumors to facilitate immune evasion [NIH, PubMed]. Upon ligand binding, ILT2 and ILT4 signal through cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to recruit phosphatases like SHP-1, thereby dampening activating signals and suppressing immune effector functions [PubMed]. In the tumor microenvironment, these receptors contribute to the polarization of macrophages toward a pro-tumorigenic M2-like phenotype and inhibit the cytolytic activity of T and NK cells [Frontiers in Immunology]. Therapeutic blockade of the ILT2/ILT4 axis, using monoclonal or bispecific antibodies like NGM707 or MK-4830, aims to reverse this suppression, promote myeloid reprogramming, and enhance anti-tumor immunity [ClinicalTrials.gov, Merck]. These agents have shown promise in clinical trials, often demonstrating synergistic effects when combined with PD-1/PD-L1 inhibitors to overcome resistance in advanced solid tumors [ASCO, ESMO]. Beyond oncology, these receptors are also implicated in viral immune evasion and the maintenance of maternal-fetal tolerance [PubMed, NIH].

Other names

ILT2ILT4LILRB1LILRB2CD85jCD85dLIR-1LIR-2MIR-7MIR-10

Antagonism of inhibitory signaling by blocking the interaction between LILRB1/LILRB2 and their ligands (e.g., HLA-G, MHC-I), thereby restoring immune cell activation, enhancing phagocytosis, and promoting pro-inflammatory myeloid reprogramming.