LILRB3 (leukocyte immunoglobulin-like receptor B3) is an inhibitory immune checkpoint protein belonging to the LILR family, which regulates immune responses by transmitting suppressive signals. Expressed primarily on myeloid cells, such as monocytes, macrophages, and dendritic cells, LILRB3 interacts with MHC class I molecules and other ligands to modulate immune tolerance and inflammatory processes. In cancer, LILRB3 is often exploited by tumors to evade immune surveillance; its activation dampens anti-tumor immunity by inhibiting myeloid cell activation, cytokine production, and T-cell responses.
LILRB3-targeting antibodies are being explored as immunotherapies to block this inhibitory pathway. Preclinical studies suggest that antagonistic anti-LILRB3 antibodies can reprogram immunosuppressive myeloid cells, enhance antigen presentation, and synergize with existing therapies like PD-1/PD-L1 inhibitors. These antibodies may also have applications in autoimmune or inflammatory diseases by fine-tuning excessive immune activation. Current research focuses on optimizing antibody specificity, efficacy, and safety profiles. Early-phase clinical trials are underway to evaluate their potential in solid tumors and hematologic malignancies. Challenges include understanding ligand diversity, receptor cross-talk, and biomarker identification for patient stratification. Overall, LILRB3 antibodies represent a promising avenue for overcoming immune suppression in the tumor microenvironment.