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The MHC class I-LILRB1 signalling axis as a promising target in cancer therapy.
- Source :
-
Scandinavian journal of immunology [Scand J Immunol] 2019 Nov; Vol. 90 (5), pp. e12804. Date of Electronic Publication: 2019 Jul 23. - Publication Year :
- 2019
-
Abstract
- Immune checkpoint inhibitors are among the newest, cutting-edge methods for the treatment of cancer. Currently, they primarily influence T cell adaptive immunotherapy targeting the PD-1/PD-L1 and CTLA-4/B7 signalling pathways. These inhibitors fight cancer by reactivating the patient's own adaptive immune system, with good results in many cancers. With the discovery of the "Don't Eat Me" molecule, CD47, antibody-based drugs that target the macrophage-related innate immunosuppressive signalling pathway, CD47-SIRPα, have been developed and have achieved stunning results in the laboratory and the clinic, but there remain unexplained instances of tumour immune escape. While investigating the immunological tolerance of cancer to anti-CD47 antibodies, a second "Don't Eat Me" molecule on tumour cells, beta 2 microglobulin (β2m), a component of MHC class I, was described. Some tumour cells reduce their surface expression of MHC class I to escape T cell recognition. However, other tumour cells highly express β2m complexed with the MHC class I heavy chain to send a "Don't Eat Me" signal by binding to leucocyte immunoglobulin-like receptor family B, member 1 (LILRB1) on macrophages, leading to a loss of immune surveillance. Investigating the mechanisms underlying this immunosuppressive MHC class I-LILRB1 signalling axis in tumour-associated macrophages will be useful in developing therapies to restore macrophage function and control MHC class I signalling in patient tumours. The goal is to promote adaptive immunity while suppressing the innate immune response to tumours. This work will identify new therapeutic targets for the development of pharmaceutical-based tumour immunotherapy.<br /> (© 2019 The Foundation for the Scandinavian Journal of Immunology.)
- Subjects :
- Adaptive Immunity immunology
Histocompatibility Antigens Class I immunology
Humans
Immunity, Innate immunology
Macrophages immunology
Signal Transduction immunology
T-Lymphocytes immunology
Antigens, CD immunology
Immune Tolerance immunology
Leukocyte Immunoglobulin-like Receptor B1 immunology
Neoplasms therapy
Tumor Escape immunology
beta 2-Microglobulin immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-3083
- Volume :
- 90
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Scandinavian journal of immunology
- Publication Type :
- Academic Journal
- Accession number :
- 31267559
- Full Text :
- https://doi.org/10.1111/sji.12804