In 2016 and 2017, monoclonal antibodies targeting PD-L1, including atezolizumab, 
durvalumab, and avelumab, were approved by the FDA for the treatment of multiple 
advanced cancers. And many other anti-PD-L1 antibodies are under clinical 
trials. Recently, the crystal structures of PD-L1 in complex with BMS-936559 and 
avelumab have been determined, revealing details of the antigen-antibody 
interactions. However, it is still unknown how atezolizumab and durvalumab 
specifically recognize PD-L1, although this is important for investigating novel 
binding sites on PD-L1 targeted by other therapeutic antibodies for the design 
and improvement of anti-PD-L1 agents. Here, we report the crystal structures of 
PD-L1 in complex with atezolizumab and durvalumab to elucidate the precise 
epitopes involved and the structural basis for PD-1/PD-L1 blockade by these 
antibodies. A comprehensive comparison of PD-L1 interactions with anti-PD-L1 
antibodies provides a better understanding of the mechanism of PD-L1 blockade as 
well as new insights into the rational design of improved anti-PD-L1 
therapeutics.