Xu Lijun, Wang Shanlong, Li Jufeng, Li Jie, Li Bingyu
College of Medical, Henan University of Science and Technology, Luoyang, Henan, China.
Department of Clinical Laboratory, The Second Affiliated Hospital of Henan University of Science and Technology, Luoyang, Henan, China.
Oncoimmunology. 2020 Apr 7;9(1):1740477. doi: 10.1080/2162402X.2020.1740477.
The leukocyte-associated immunoglobulin-like receptor 1 (LAIR-1) is an inhibitory receptor expressed on the majority of peripheral blood mononuclear cells and is important for the regulation of immune responses. The binding of LAIR-1 to its ligands results in the loss of immune function in the tumor microenvironment (TME) and a reduction in T cell function and immune responses of antigen-presenting cells. Using bioinformatics analysis, we showed that LAIR-1 is broadly upregulated in multiple types of cancer. By designing a LAIR-2-Fc recombinant protein to block the binding of LAIR-1 to its ligand collagen, we observed augmented cytotoxic T cell infiltration and function resulting in antitumor immune responses that eliminated cancer cells. Besides, LAIR-2-Fc fusion protein potentiated the antitumor effect of PD-1/L1 checkpoint blockade therapy. Collectively, our results support the targeting of LAIR-1 for potential immunotherapeutic applications.
白细胞相关免疫球蛋白样受体1（LAIR-1）是一种在大多数外周血单核细胞上表达的抑制性受体，对免疫反应的调节很重要。LAIR-1与其配体结合会导致肿瘤微环境（TME）中免疫功能丧失以及T细胞功能和抗原呈递细胞免疫反应降低。通过生物信息学分析，我们发现LAIR-1在多种癌症中广泛上调。通过设计LAIR-2-Fc重组蛋白来阻断LAIR-1与其配体胶原蛋白的结合，我们观察到细胞毒性T细胞浸润和功能增强，从而产生消除癌细胞的抗肿瘤免疫反应。此外，LAIR-2-Fc融合蛋白增强了PD-1/L1检查点阻断疗法的抗肿瘤作用。总体而言，我们的结果支持将LAIR-1作为潜在免疫治疗应用的靶点。
Zotero 插件
