LILRB2 (ILT4)

Class

Anti-LILRB2 IgG1 monoclonal antibody

Pathway

Myeloid immune-checkpoint blockade (tested alone and with cemiplimab, an anti-PD-1)

LILRB2, also called ILT4, is an inhibitory receptor found on monocytes, macrophages, and dendritic cells—the myeloid arm of the immune system. It belongs to the leukocyte immunoglobulin-like receptor family and, upon engaging ligands such as certain MHC class I molecules and angiopoietin-like proteins, delivers a signal that keeps these cells in a quiescent, tolerance-promoting state. In tumors, this pathway is frequently exploited: tumor-associated macrophages skewed toward an immunosuppressive phenotype dampen local anti-tumor immunity and provide cover for cancer cells to evade destruction. Blocking LILRB2 with a monoclonal antibody aims to relieve this brake, shifting myeloid cells toward a more inflammatory, antigen-presenting state that can better activate T cells. Because this is a distinct checkpoint from the well-known PD-1/PD-L1 axis, which acts directly on T cells, LILRB2 blockade is often studied in combination with T-cell checkpoint inhibitors, on the premise that reprogramming the myeloid compartment and unleashing T-cell activity act on complementary parts of the tumor immune evasion program. This mechanism is broadly relevant to solid tumors where dense macrophage infiltration and immunosuppressive myeloid populations are thought to limit the effectiveness of T-cell-directed immunotherapies alone.