Perspectives of targeting LILRB1 in innate and adaptive immune checkpoint therapy of cancer

Frontiers in Immunology

Immunology

Ira A. Münnich¹  Patricia Hilger¹  Andreas Humpe¹  Christian Kellner¹  Tobias Zeller¹  Roland Windisch¹  Denis M. Schewe² 

[1] Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, University Hospital, LMU Munich, Munich, Germany;Medical Faculty, Otto-von-Guericke University Magdeburg, Magdeburg, Germany;

关键词: LILRB1 (ILT2);    macrophages;    cancer;    phagocytosis;    immune checkpoint blockade;    antibody therapy;    NK cells;    T cells;   

DOI  :  10.3389/fimmu.2023.1240275

 received in 2023-06-14, accepted in 2023-08-08,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Zeller, Münnich, Windisch, Hilger, Schewe, Humpe and Kellner