1. Imaging and quantifying analysis the binding behavior of PD-L1 at molecular resolution by atomic force microscopy.
- Author
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Qin, Juan, Zhang, Miaomiao, Guan, Yanxue, Guo, Xinyue, Li, Zongjia, Rankl, Christian, and Tang, Jilin
- Subjects
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PROGRAMMED death-ligand 1 , *ATOMIC force microscopy , *SINGLE molecules , *IMAGE analysis , *BEHAVIORAL assessment , *NUCLEAR forces (Physics) , *PROGRAMMED cell death 1 receptors - Abstract
Immunotherapy has emerged as an effective treatment modality for cancer. The interaction of programmed cell death ligand-1 (PD-L1) and programmed cell death protein-1 (PD-1) plays a key role in tumor-related immune escape and has become one of the most extensive targets for immunotherapy. Herein, we investigated the interaction of PD-L1 with its antibody and PD-1 using atomic force microscopy-based single molecule force spectroscopy for the first time. It was found that the PD-L1/anti-PD-L1 antibody complex was easier to dissociate than PD-L1/PD-1. The unbinding forces of specific interaction of PD-L1 on T24 cells with its antibody and PD-1 were quantitatively measured and similar to those on substrate. In addition, the location of PD-L1 on T24 cells was mapped at the single-molecule level by force-volume mapping. The force maps revealed that PD-L1 randomly distributed on T24 cells surface. The recognition events on cells obviously increased after INF-γ treatment, which proved that INF-γ up-regulated the expression of PD-L1 on T24 cells. These findings enrich our understanding of the molecular mechanisms by which PD-L1 interacts with its antibody and PD-1. It provides useful information for the physical factors that is needed to be considered in the design of inhibitors for tumor immunology. [Display omitted] • The interaction of PD-L1 with its antibody and PD-1 was investigated by AFM. • The distribution of PD-L1 on cells was visualized at the single-molecule level. • The effect of INF-γ on PD-L1 expression on cells was quantitatively characterized. • This work provides new insights into the biophysical properties of PD-L1. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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