Table 1.
Potential mechanisms for a tumor biopsy to be labeled as PD-L1 positive or negative
PD-L1 status and significanceCell type/types being positive or negative for PD-L1Examples of mechanismsReferences
Positive    
Genetic process Cancer cells PDJ amplicon Ansell et al., 2015  
  MYC Casey et al., 2016  
  PDL1 3′-UTR disruption Kataoka et al., 2016  
  CDK5 disruption Dorand et al., 2016  
  Mutant EGFR Akbay et al., 2013  
  PTEN deletion Parsa et al., 2007  
  PI3K/AKT mutations Lastwika et al., 2016  
Reactive to a T cell infiltrate Cancer and immune cells/stromal cells in the tumor microenvironment IFN-γ induced upon tumor antigen–specific T cell infiltration Lee et al., 2006; Taube et al., 2012; Herbst et al., 2014; Tumeh et al., 2014  
Negative    
Genetic process Cancer cells JAK1 or JAK2 truncating mutations Shin, D.S., et al. 2015. Proceedings of the 106th Annual Meeting of the American Association for Cancer Research. Abstr. 5013; Zaretsky et al., 2016  
Absence of a T cell infiltrate Cancer and immune cells/stromal cells in the tumor microenvironment No T cells in the tumor Herbst et al., 2014; Tumeh et al., 2014  
PD-L1 status and significanceCell type/types being positive or negative for PD-L1Examples of mechanismsReferences
Positive    
Genetic process Cancer cells PDJ amplicon Ansell et al., 2015  
  MYC Casey et al., 2016  
  PDL1 3′-UTR disruption Kataoka et al., 2016  
  CDK5 disruption Dorand et al., 2016  
  Mutant EGFR Akbay et al., 2013  
  PTEN deletion Parsa et al., 2007  
  PI3K/AKT mutations Lastwika et al., 2016  
Reactive to a T cell infiltrate Cancer and immune cells/stromal cells in the tumor microenvironment IFN-γ induced upon tumor antigen–specific T cell infiltration Lee et al., 2006; Taube et al., 2012; Herbst et al., 2014; Tumeh et al., 2014  
Negative    
Genetic process Cancer cells JAK1 or JAK2 truncating mutations Shin, D.S., et al. 2015. Proceedings of the 106th Annual Meeting of the American Association for Cancer Research. Abstr. 5013; Zaretsky et al., 2016  
Absence of a T cell infiltrate Cancer and immune cells/stromal cells in the tumor microenvironment No T cells in the tumor Herbst et al., 2014; Tumeh et al., 2014  

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