Search

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]