Human pathology
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One of the major breakthroughs in oncology in the past decade has been the research and development of immune checkpoint inhibitors. Since the discovery of the PD-1/PD-L1 axis as a key mediator in peripheral self-tolerance and the subsequent discovery of its role promoting immune escape in cancers, the PD-1/PD-L1 pathway has produced considerable excitement from both a scientific and therapeutic standpoint. The past decade has seen an explosion in the number of clinical trials utilizing anti-PD-1/PD-L1 therapy. ⋯ However, many open questions remain in a rapidly changing therapeutic and scientific landscape. In this review, we describe the basic functioning of the PD-1/PD-L1 axis in normal biology, how it is coopted by cancers to promote immune escape, and then review the literature regarding the prognostic value of tumoral PD-L1 expression on its own before discussing recent therapeutic advances, and the emerging role for pathologists in predicting response to anti-PD-1/PD-L1 therapies. Special attention is given to melanoma and non-small cell lung cancer, malignancies that have seen the broadest applications of anti-PD-L1/PD-1 therapies.