Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies

• Main Authors: Shuguang Tan, Danqing Chen, Kefang Liu, Mengnan He, Hao Song, Yi Shi, Jun Liu, Catherine W.-H. Zhang, Jianxun Qi, Jinghua Yan, Shan Gao, George F. Gao
• Format: Article
• Language: English
• Published: SpringerOpen 2016-11-01
• Series: Protein & Cell
• Subjects: PD-1/PD-L1 interaction; checkpoint blockade; molecular basis; therapeutic antibody
• Online Access: http://link.springer.com/article/10.1007/s13238-016-0337-7
• ISSN: 1674-800X; 1674-8018

Abstract Antibody-based PD-1/PD-L1 blockade therapies have taken center stage in immunotherapies for cancer, with multiple clinical successes. PD-1 signaling plays pivotal roles in tumor-driven T-cell dysfunction. In contrast to prior approaches to generate or boost tumor-specific T-cell responses, antibody-based PD-1/PD-L1 blockade targets tumor-induced T-cell defects and restores pre-existing T-cell function to modulate antitumor immunity. In this review, the fundamental knowledge on the expression regulations and inhibitory functions of PD-1 and the present understanding of antibody-based PD-1/PD-L1 blockade therapies are briefly summarized. We then focus on the recent breakthrough work concerning the structural basis of the PD-1/PD-Ls interaction and how therapeutic antibodies, pembrolizumab targeting PD-1 and avelumab targeting PD-L1, compete with the binding of PD-1/PD-L1 to interrupt the PD-1/PD-L1 interaction. We believe that this structural information will benefit the design and improvement of therapeutic antibodies targeting PD-1 signaling.