关键词: Programmed death-ligand 1, 淋巴管畸形, 大鼠模型

Abstract: Objective: To observe the effect of Anti-PD-L1 therapy in established LMs rat models. Methods: LMs rat models were established by injection of Freund's incomplete adjuvant (FIA) in subcutaneous to the neck in twenty female Wistar rats [(250 ± 30) g]. Rats with lesions were randomly divided into four groups with different treatment as follows: PBS only, PBS and Anti-PD-L1, PBS and LPS or PBS combination with LPS and Anti-PD-L1. The sizes of LMs lesions and body weight of rats were measured for every week. After eight weeks, all rats were euthanized and the cystic lesions and vital visceral organs were harvested for further investigation. Expression level of PD-L1 in normal skins and human LMs was detected by immunohistochemistry. Results: PD-L1 was strongly elevated in the LM lesions of rats and further increased in the presence of LPS. Anti-PD-L1 therapy showed satisfactory therapeutic effect on both non-inflammatory and inflammatory LMs by decreasing the proliferation and tubular formation of lymphatic endothelial cells. In addition, compared with normal skins, PD-L1 was also upregulated in human LM lesions. Conclusion: PD-L1 might contribute to the pathological process of lymphatic malformations. Targeting the PD-L1 might be a promising therapeutic strategy for LMs.

Key words: programmed death-ligand 1, lymphatic malformations, rat models