Ig-like transcript 2 and Ig-like transcript 4 (ILT2 and ILT4)

Ig-like transcript 2 (ILT2, LILRB1, CD85j) and Ig-like transcript 4 (ILT4, LILRB2, CD85d) are inhibitory receptors of the LILR family, structurally characterized as immunoglobulin superfamily proteins with immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in their cytoplasmic domains[1][2][6]. ILT2 is broadly expressed on multiple immune cell types, including T cells, natural killer (NK) cells, B cells, monocytes, macrophages, dendritic cells, and some granulocytes, while ILT4 is mainly expressed on myelomonocytic cells such as monocytes and dendritic cells[1][2][6]. Both receptors recognize a range of classical and nonclassical MHC class I molecules, with preferential high-affinity binding to HLA-G[1][2]. Their primary biological function is immune inhibition: upon ligand engagement, ITIMs in their cytoplasmic tails recruit SHP-1/SHP-2 phosphatases, dampening activating signals and reducing cell activation, cytokine production, antigen presentation, and cytotoxic functions[1][2][3][6]. In the tumor microenvironment, ILT2 and ILT4 contribute to immune suppression, and blockade of these receptors synergistically reprograms myeloid cells, enhances dendritic cell and macrophage activation, and promotes a shift to a pro-inflammatory M1 phenotype[3][4][5]. Clinical and preclinical evidence supports their roles as therapeutic checkpoints in immuno-oncology, where dual inhibition may overcome tumor-mediated immunosuppression and aid response to other therapies[3][4][5]. Expresión of these receptors (and biomarkers such as CD86, CD163, CXCL9, and CCL5) may predict therapeutic response and inform patient selection[3][4]. Safety concerns include the potential for overactivation and loss of immune tolerance when these pathways are inhibited[5][6].

Other names

Leukocyte immunoglobulin-like receptor 1 (LILRB1)CD85jLeukocyte immunoglobulin-like receptor 2 (LILRB2)CD85dLIR-1LIR-2immunoglobulin-like transcriptleukocyte inhibitory receptor

Blockade of inhibitory signaling (disrupts ITIM signaling and SHP1/SHP2 recruitment); Immune checkpoint inhibition (releases suppression of myeloid/lymphoid cells, enhances antitumor immunity); Promotion of M1 macrophage polarization and cytotoxic T cell activity