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.
mRNA Expression Analysis
The hPD-L1, but not mPD-L1, mRNA was detectable in splenocytes of the homozygous B-hPD-L1 mice.
Protein Expression Analysis
Cells in ascites from both wild type (WT)C57BL/6 and homozygous B-hPD-L1 mice were analyzed by flow cytometry. Mouse PD-L1 + B cells were detectable in the WT mice, while human PD-L1 + B cells were detectable in the homozygous B-hPD-L1 mice.
Splenocytes from both wild type (WT)C57BL/6 and homozygous B-hPD-L1 mice were analyzed by flow cytometry. Mouse PD-L1 + T cells were detectable in the WT mice, while human PD-L1 + T cells were detectable in the homozygous B-hPD-L1 mice.
PD-L1(Tecentriq) Efficacy Evaluation
Modified murine colon cancer MC38 cells (mPD-L1 extracellular domain is replaced with the hPD-L1 extracellular domain, named as MC38-hPD-L1) were subcutaneously implanted into homozygous B-hPD-L1 mouse. Mice were divided into control and experimental groups (n=5) when the tumor size was about 100 mm3. Anti-hPD-L1 antibody Tencentiq (Atezolizumab) significantly inhibited tumor growth in the homozygous B-hPD-L1 mice at 3 different doses, suggesting that MC38-hPD-L1 cells in B-hPD-L1 mice is an effective model for in vivo hPD-L1 antibody efficacy study. (A) Tumor average volume ± SEM, (B) Mice average weight ± SEM.
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