LILRB

LILRB is a type I transmembrane glycoprotein belonging to the leukocyte immunoglobulin-like receptor (LILR) family, also known as the CD85, ILT, or LIR family. It is an immunosuppressive receptor. Its structure consists of an extracellular, transmembrane, and intracellular region: the extracellular region contains four immunoglobulin (Ig)-like domains responsible for ligand binding; the intracellular region contains the immunoreceptor tyrosine inhibitory motif (ITIM), a key region for transmitting inhibitory signals. This family contains five members (LILRB1-LILRB5).
LILRB binds to ligands such as MHC-l, ApoE, and Angptls, inducing ITIM tyrosine phosphorylation, thereby recruiting SHP-1/SHP-2 and SHIP phosphatases to dephosphorylate downstream kinases (Src, Syk, ZAP70, PI3K, etc.), ultimately inhibiting the activation, proliferation, and cytotoxicity of immune cells (such as T cells, NK cells, and macrophages), and promoting tumor immune escape. LILRB targets possess a unique mechanism of action, offering novel strategies for overcoming tumor immunotherapy challenges.
LILRBs are highly expressed in various solid tumors (such as lung cancer, breast cancer, and liver cancer) and hematological malignancies (such as acute myeloid leukemia and multiple myeloma), and are associated with tumor progression, immune escape, and poor prognosis. Meanwhile, members such as LILRB4 are abnormally expressed in autoimmune diseases such as systemic lupus erythematosus and Kawasaki disease, participating in immune tolerance and inflammation regulation. Monoclonal antibodies, CAR-T cells, and ADCs have entered clinical trials, and combining them with PD-1 inhibitors is becoming an important direction.