Journal
PROTEIN & CELL
Volume 7, Issue 12, Pages 866-877Publisher
SPRINGEROPEN
DOI: 10.1007/s13238-016-0337-7
Keywords
PD-1/PD-L1 interaction; checkpoint blockade; molecular basis; therapeutic antibody
Categories
Funding
- National Basic Research Program (973 Program) [2013CB531502, 2014CB542503]
- National Natural Science Foundation of China [31390432, 31500722]
- Grand S&T project of China Health and Family Planning Commission [2013ZX10004608-002, 2016ZX10004201-009]
- Strategic Priority Research Program of the Chinese Academy of Sciences (CAS) [XDB08020100]
- NSFC Innovative Research Group [81321063]
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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.
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