Leukocyte immunoglobulin-like receptor subfamily B member 1, member 2, and Killer cell immunoglobulin-like receptor 2DL4 (ILT2/ILT4/KIR2DL4)

ILT2 (LILRB1), ILT4 (LILRB2), and KIR2DL4 are a group of inhibitory receptors primarily expressed on immune cells that serve as the cognate receptors for the non-classical MHC class I molecule, HLA-G. While ILT2 is broadly expressed on B cells, NK cells, and subsets of T cells, ILT4 is predominantly found on myeloid cells such as macrophages and dendritic cells, and KIR2DL4 is mainly restricted to NK cells. In physiological conditions, the interaction between HLA-G and these receptors is crucial for maintaining immune tolerance, particularly at the maternal-fetal interface to prevent fetal rejection. However, in the context of malignancy, tumors often overexpress HLA-G to hijack this pathway, leading to the suppression of NK and T cell cytotoxicity and the induction of a tolerogenic, immunosuppressive myeloid microenvironment. Therapeutic strategies targeting this axis, such as dual ILT2/ILT4 antagonists like NGM707 or selective inhibitors like BND-22, aim to "release the brakes" on the immune system by blocking these inhibitory signals, thereby promoting tumor cell phagocytosis and enhancing adaptive anti-tumor responses.

Other names

LILRB1LILRB2CD158dCD85jCD85dLeukocyte immunoglobulin-like receptor subfamily B member 1Leukocyte immunoglobulin-like receptor subfamily B member 2Killer cell immunoglobulin-like receptor 2DL4HLA-G receptorsLIR-1LIR-2MIR-7MIR-10

Antagonism of inhibitory signaling by blocking the interaction between HLA-G (and other MHC-I molecules) and their receptors on immune cells, thereby restoring the activity of NK cells, T cells, and myeloid cells.