Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) (LAIR1)

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR1) is a transmembrane inhibitory receptor belonging to the immunoglobulin superfamily, primarily expressed on the surface of various immune cells, including T cells, NK cells, and myeloid cells (UniProt Q6GTX8). LAIR1 functions as an immune checkpoint by binding to collagen ligands, such as Collagen IV, which are frequently overexpressed in the tumor microenvironment (TME). This interaction triggers inhibitory signaling through immunoreceptor tyrosine-based inhibitory motifs (ITIMs), leading to the suppression of immune cell activation and facilitating tumor immune evasion (PubMed: 32814575). LAIR2 is a soluble homolog of LAIR1 that acts as a natural decoy by binding to collagen with higher affinity, thereby preventing LAIR1-mediated inhibition (UniProt Q6ISS4). Therapeutic agents like NC-410, a LAIR2-Fc fusion protein, are designed to mimic this natural mechanism by competitively binding to Collagen IV, effectively blocking the LAIR1-collagen axis and restoring the anti-tumor activity of the immune system (NextCure, Inc.).

Other names

CD305Leukocyte-associated Ig-like receptor 1LAIR-1

Competitive inhibition of the LAIR1-collagen interaction using a LAIR2-based decoy protein to prevent immune suppression in the tumor microenvironment.