The LILRB family in hematologic malignancies: prognostic associations, mechanistic considerations, and therapeutic implications

The leukocyte immunoglobulin-like receptor B (LILRB) proteins, characterized by their transmembrane nature and canonical immunoreceptor tyrosine-based inhibitory motifs (ITIM) signaling, play a pivotal role in maintaining immune homeostasis and are implicated in the pathogenesis of various disease states. This comprehensive review will focus on the intricate involvement of the LILRB family in hematologic malignancies. These receptors have emerged as valuable diagnostic and prognostic biomarkers in leukemia, lymphoma, and myeloma. Beyond their prognostic implications, LILRBs actively shape the immune microenvironment and directly influence the disease pathogenesis of hematologic malignancies. Furthermore, their identification as potential therapeutic targets offer a promising avenue for precision medicine strategies in the treatment of these disorders. Currently, multiple LILRB directed therapies are in the preclinical and clinical trial pipelines. This review underscores the multifaceted role of the LILRB family in hematologic malignancies, highlighting their significance from diagnostic and prognostic perspectives to their broader impact on disease pathophysiology and as valuable therapeutic targets.