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

Leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1), also known as CD305, is a transmembrane inhibitory receptor expressed on the majority of peripheral blood mononuclear cells, including T cells, B cells, NK cells, and myeloid cells (UniProt P98023). It functions as an immune checkpoint by binding to various types of collagen, which serve as its functional ligands in the extracellular matrix (PubMed: 16551250). Upon collagen binding, LAIR-1 signals through its cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs) to recruit phosphatases like SHP-1 and SHP-2, which downregulate activating signals within the immune cell (PubMed: 9285411). In the context of cancer, tumors often produce an abundance of collagen, creating a suppressive microenvironment that exploits the LAIR-1 pathway to evade immune destruction (PubMed: 31110139). Therapeutic targeting of the Collagen–LAIR-1 interface aims to disrupt this inhibitory axis, thereby restoring the ability of the immune system to attack tumor cells. Current clinical candidates include NC410, a LAIR-2-Fc fusion protein that acts as a decoy to sequester collagen, and NC762, a monoclonal antibody that directly blocks LAIR-1 (NextCure). These therapies are primarily being investigated for their potential to treat solid tumors that exhibit high collagen density or significant immune infiltration.

Other names

CD305LAIR1Leukocyte-associated Ig-like receptor 1Collagen receptor LAIR-1

Blockade of the inhibitory interaction between collagen ligands and the LAIR-1 receptor to restore immune cell activity.