1. LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation.
- Author
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Jiang Z, Huang Q, Chang Y, Qiu Y, Cheng H, Yang M, Ruan S, Ji S, Sun J, Wang Z, Xu S, Liang R, Dai X, Wu K, Li B, Li D, and Zhao H
- Subjects
- Humans, Animals, Female, Cell Line, Tumor, Mice, Ubiquitination, Membrane Glycoproteins metabolism, Proteolysis, Middle Aged, CD8-Positive T-Lymphocytes immunology, CD8-Positive T-Lymphocytes metabolism, Ubiquitin-Protein Ligases metabolism, Ubiquitin-Protein Ligases genetics, Breast Neoplasms immunology, Breast Neoplasms pathology, Breast Neoplasms genetics, Breast Neoplasms metabolism, Mice, Inbred BALB C, Tumor Escape, Mice, Nude, Receptors, Immunologic metabolism
- Abstract
Purpose: Increased expression of leukocyte immunoglobulin-like receptor subfamily B member 2 (LILRB2) is associated with immune evasion in breast cancer (BC). The aim of this study to elucidate the role of LILRB2 in BC progression., Methods: LILRB2 expression in tumor tissues was detected by immunohistochemical staining. Human leukocyte antigen A (HLA-A) expression in BC cells was detected by Western blotting, and HLA-A ubiquitination was detected by immunoprecipitation and histidine pulldown assay. An in-situ tumor model was established in nude BALB/c mice to verify the role of LILRB2 in immune escape. Finally, the functions and potential mechanisms of LILRB2 in BC progression were explored using in silico data., Results: LILRB2 was upregulated in BC tissues and cells, and correlated positively with poor prognosis. LILRB2 promoted BC progression by downregulating HLA-A expression. Mechanistically, LILRB2 facilitates the ubiquitination and subsequent degradation of HLA-A by promoting the interaction between the ubiquitin ligase membrane-associated ring finger protein 9 (MARCH9) and HLA-A. In syngeneic graft mouse models, LILRB2-expressing BC cells evaded CD8 + T cells and inhibited the secretion of cytokines by the cytotoxic CD8 + T cells., Conclusion: LILRB2 downregulates HLA-A to promote immune evasion in BC cells and is a promising new target for BC treatment., (© 2024. Springer Nature Switzerland AG.)
- Published
- 2024
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