PD-L1 immunohistochemistry: current state and challenges as a companion diagnostic
This comprehensive review examines PD-L1 as the most widely validated biomarker for selecting patients for anti-PD-1/PD-L1 therapy, while detailing persistent challenges including inter-assay variability, different companion diagnostic requirements per drug, inconsistent cut-off points, and lack of prospective cross-assay comparisons. The authors discuss regulatory complexities and how future quantitative methods could improve patient selection. Essential reading for pathology labs running PD-L1 testing.
The original study
PD-L1 as a biomarker of response to immune-checkpoint inhibitors.
- Authors
- Doroshow DB, Bhalla S, Beasley MB, Sholl LM, Kerr KM, Gnjatic S, et al.
- Journal
- Nature reviews. Clinical oncology
- Type
- Journal Article, Review
- PMID
- 33580222
Original abstract
Immune-checkpoint inhibitors targeting PD-1 or PD-L1 have already substantially improved the outcomes of patients with many types of cancer, although only 20-40% of patients derive benefit from these new therapies. PD-L1, quantified using immunohistochemistry assays, is currently the most widely validated, used and accepted biomarker to guide the selection of patients to receive anti-PD-1 or anti-PD-L1 antibodies. However, many challenges remain in the clinical use of these assays, including the necessity of using different companion diagnostic assays for specific agents, high levels of inter-assay variability in terms of both performance and cut-off points, and a lack of prospective comparisons of how PD-L1+ disease diagnosed using each assay relates to clinical outcomes. In this Review, we describe the current role of PD-L1 immunohistochemistry assays used to inform the selection of patients to receive anti-PD-1 or anti-PD-L1 antibodies, we discuss the various technical and clinical challenges associated with these assays, including regulatory issues, and we provide some perspective on how to optimize PD-L1 as a selection biomarker for the future treatment of patients with solid tumours.