A new approach to the management of non-small-cell lung cancer (NSCLC) has 
recently emerged that works by manipulating the immune checkpoint controlled by 
programmed death receptor 1 (PD-1) and its ligand programmed death ligand 1 
(PD-L1). Several drugs targeting PD-1 (pembrolizumab and nivolumab) or PD-L1 
(atezolizumab, durvalumab, and avelumab) have been approved or are in the late 
stages of development. Inevitably, the introduction of these drugs will put 
pressure on healthcare systems, and there is a need to stratify patients to 
identify those who are most likely to benefit from such treatment. There is 
evidence that responsiveness to PD-1 inhibitors may be predicted by expression 
of PD-L1 on neoplastic cells. Hence, there is considerable interest in using 
PD-L1 immunohistochemical staining to guide the use of PD-1-targeted treatments 
in patients with NSCLC. This article reviews the current knowledge about PD-L1 
testing, and identifies current research requirements. Key factors to consider 
include the source and timing of sample collection, pre-analytical steps (sample 
tracking, fixation, tissue processing, sectioning, and tissue prioritization), 
analytical decisions (choice of biomarker assay/kit and automated staining 
platform, with verification of standardized assays or validation of 
laboratory-devised techniques, internal and external quality assurance, and 
audit), and reporting and interpretation of the results. This review addresses 
the need for integration of PD-L1 immunohistochemistry with other tests as part 
of locally agreed pathways and protocols. There remain areas of uncertainty, and 
guidance should be updated regularly as new information becomes available.