Programmed Death Ligand-1 (PD-L1) Expression in the Programmed Death Receptor-1 (PD-1)/PD-L1 Blockade: A Key Player Against Various Cancers

- Immune checkpoint pathways, including programmed death receptor-1/programmed death ligand-1 (PD-1/PD-L1) signaling pathway, which are important in mediating self-tolerance and controlling self-damage, can sometimes be manipulated by cancer cells to evade immune surveillance. Recent clinical trials further demonstrate the efficacy of PD-1/PD-L1-targeted therapy in various cancers and reveal a new era of cancer immunotherapy. - To review the mechanism of the PD-1/PD-L1 signaling pathway, the regulation of this pathway, PD-1/PD-L1 as a predictive and/or prognostic marker in various cancers, and strategies of measuring PD-L1 expression. - Representative medical literature regarding PD-L1 expression in various cancers, including the preliminary results of the Blue Proposal, which compares different immunohistochemical stains for PD-L1 reported in the recent American Association of Cancer Research (AACR) Annual Meeting (April 16-20, 2016). - Either PD-1/PD-L1-targeted therapy alone or in combination with other treatment modalities provides benefit for patients with advanced cancers. Because of the complexity of cancer immunity, we still do not have a reliable biomarker to predict the response of PD-1/PD-L1-targeted therapy. Future studies, including methods beyond immunohistochemical stains, are needed to develop reliable biomarker/biomarkers for pathology laboratories to aid in selecting patients who will benefit most from PD-1/PD-L1-targeted therapy.