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Media type:
E-Article
Title:
Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer
Contributor:
Zeller, Tobias;
Münnich, Ira A.;
Windisch, Roland;
Hilger, Patricia;
Schewe, Denis M.;
Humpe, Andreas;
Kellner, Christian
Published:
Frontiers Media SA, 2023
Published in:
Frontiers in Immunology, 14 (2023)
Language:
Not determined
DOI:
10.3389/fimmu.2023.1240275
ISSN:
1664-3224
Origination:
Footnote:
Description:
Immune checkpoint blockade is a compelling approach in tumor immunotherapy. Blocking inhibitory pathways in T cells has demonstrated clinical efficacy in different types of cancer and may hold potential to also stimulate innate immune responses. A novel emerging potential target for immune checkpoint therapy is leukocyte immunoglobulin-like receptor subfamily B member 1 (LILRB1). LILRB1 belongs to the superfamily of leukocyte immunoglobulin-like receptors and exerts inhibitory functions. The receptor is expressed by a variety of immune cells including macrophages as well as certain cytotoxic lymphocytes and contributes to the regulation of different immune responses by interaction with classical as well as non-classical human leukocyte antigen (HLA) class I molecules. LILRB1 has gained increasing attention as it has been demonstrated to function as a phagocytosis checkpoint on macrophages by recognizing HLA class I, which represents a ‘Don’t Eat Me!’ signal that impairs phagocytic uptake of cancer cells, similar to CD47. The specific blockade of the HLA class I:LILRB1 axis may provide an option to promote phagocytosis by macrophages and also to enhance cytotoxic functions of T cells and natural killer (NK) cells. Currently, LILRB1 specific antibodies are in different stages of pre-clinical and clinical development. In this review, we introduce LILRB1 and highlight the features that make this immune checkpoint a promising target for cancer immunotherapy.