LILRB2 promotes immune escape in breast cancer cells via enhanced HLA-A degradation

期刊论文
发表日期：

2024年4月24日

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Zhiyuan Jiang,
Qianru Huang,
Yujie Chang,
Yiran Qiu,
Hao Cheng,
Mengdi Yang,
Shunyi Ruan,
Suyuan Ji,
Jing Sun,
Zhiyu Wang,
Shengyuan Xu,
Rui Liang,
Xueyu Dai,
Kejin Wu,
Bin Li,
Dan Li,
Hui Zhao

摘要

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.