Non–Small Cell Lung Cancer, PD-L1, and the Pathologist

Abstract

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.