PD-L1 (Programmed cell death ligand-1), also known as B7-H1 and CD274, is mainly expressed in antigen-presenting cells (APCs) and activated T cells, and is one of the two ligands of PD-1. The interaction between PD1 and PD-L1 plays an important role in the negative regulation of the immune response. PD-L1 is highly expressed in a variety of solid tumors. PD-1 and PD-L1 interactions can reduce T Cell Activation and promote tumor immune escape. The PD-1/PD-L1 signaling pathway can be blocked and antitumor immune response can be restored by using by anti-PD-1 or anti-PD-L1 antibodies to block the binding of PD1 to PD-L1. T-cell immunoglobulin domain and mucin domain-3 (TIM3) is an activation-induced inhibitory molecule involved in immune tolerance and T-cell exhaustion in chronic viral infection and cancers. TIM3 maturation and cell surface expression is facilitated by forming a heterodimeric interaction with CD66a. Co-blockade of CD66a and TIM3 enhanced anti-tumor immune responses, and eliminated tumors in mouse colorectal cancer models.
Gene targeting strategy of B-hPD-L1/hTIM3 mice. The targeting strategy of B-hPD-L1 mice is to the exon 3 of mouse PD-L1 gene that encode the extracellular domain were replaced by human PD-L1 exon 3. The targeting strategy of B-hTIM3 mice is to the exon 2 of mouse Tim3 gene that encode the extracellular domain were replaced by human TIM3 exon 2 . The B-hPD-L1/hTIM3 double knock-in model, was developed by breeding the B-hPD-L1 mice and the B-hTIM3 mice, has a functional mouse immune system.
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- Int. J. Mol. Sci. 2017, 18, 645; doi:10.3390/ijms18030645