PD-L1 Testing in Non-small Cell Lung Cancer: Past, Present, and Future

Blockade of the programmed cell death-1 (PD-1) axis has already been established as an effective treatment of non-small cell lung cancer. Immunohistochemistry (IHC) for programmed death-ligand 1 (PD-L1) protein is the only available biomarker that can guide treatment with immune checkpoint inhibitors in non-small cell lung cancer. Because each PD-1/PD-L1 blockade was approved together with a specific PD-L1 IHC assay used in the clinical trials, pathologists have been challenged with performing various assays with a limited sample. To provide a more unified understanding of this, several cross-validation studies between platforms have been performed and showed consistent results. However, the interchangeability of assays may be limited in practice because of the risk of misclassification of patients for the treatment. Furthermore, several issues, including the temporal and spatial heterogeneity of PD-L1 expression in the tumor, and the potential for cytology specimens to be used as an alternative to tissue samples for PD-L1 testing, have still not been resolved. In the future, one of the main aims of immunotherapy research should be to find a novel predictive biomarker for PD-1 blockade therapy and a way to combine it with PD-L1 IHC and other tests.