CONTEXT: Although most primary cancers of the lung carry a heavy mutational load 
and will potentially present many "nonself" antigens to the immune system, there 
are a wide range of possible mechanisms for tumors to avoid so-called immune 
surveillance. One such mechanism is the adoption of immune checkpoints to 
inhibit the host immune response. Immune checkpoint inhibitors show great 
promise in the treatment of advanced non-small cell lung cancer.
OBJECTIVE: To discuss the possibility of biomarker selection of patients for 
these therapies. This is becoming a much debated issue, and the 
immunohistochemical detection of Programmed Death Ligand 1 (PD-L1), the ligand 
for the inhibitory Programmed Death receptor 1 (PD-1) checkpoint, is one 
possible biomarker. Data so far available show some conflicting results, but 
PD-L1 immunohistochemistry looks likely to be introduced into clinical use for 
selecting patients for treatment with anti-PD-1 or anti-PD-L1 therapies. Given 
that there are 4 such drugs rapidly approaching regulatory approval, each with 
its own independent PD-L1 immunohistochemistry biomarker test, both oncologists 
and pathologists face some significant challenges.
DATA SOURCES: Peer-reviewed literature and meeting proceedings, especially 
during the last 12 months, were used.
CONCLUSIONS: The biology of PD-1/PD-L1 is complex, the clinical data for these 
drugs show considerable variation, the selection performance of the PD-L1 
biomarker test is not perfect, and the existence of 4 drug/test combinations 
adds significantly to the problems faced. This article addresses some of the 
background to this therapeutic problem and discusses some of the issues ahead.