Programmed death ligand-1 (PD-L1) as a predictive marker for immunotherapy in solid tumours: a guide to immunohistochemistry implementation and interpretation

Pathology. 2021 Feb;53(2):141-156. doi: 10.1016/j.pathol.2020.10.007. Epub 2020 Dec 30.

Abstract

Immunotherapy with checkpoint inhibitors is well established as an effective treatment for non-small cell lung cancer and melanoma. The list of approved indications for treatment with PD-1/PD-L1 checkpoint inhibitors is growing rapidly as clinical trials continue to show their efficacy in patients with a wide range of solid tumours. Clinical trials have used a variety of PD-L1 immunohistochemical assays to evaluate PD-L1 expression on tumour cells, immune cells or both as a potential biomarker to predict response to immunotherapy. Requests to pathologists for PD-L1 testing to guide choice of therapy are rapidly becoming commonplace. Thus, pathologists need to be aware of the different PD-L1 assays, methods of evaluation in different tumour types and the impact of the results on therapeutic decisions. This review discusses the key practical issues relating to the implementation of PD-L1 testing for solid tumours in a pathology laboratory, including evidence for PD-L1 testing, different assay types, the potential interchangeability of PD-L1 antibody clones and staining platforms, scoring criteria for PD-L1, validation, quality assurance, and pitfalls in PD-L1 assessment. This review also explores PD-L1 IHC in solid tumours including non-small cell lung carcinoma, head and neck carcinoma, triple negative breast carcinoma, melanoma, renal cell carcinoma, urothelial carcinoma, gastric and gastroesophageal carcinoma, colorectal carcinoma, hepatocellular carcinoma, and endometrial carcinoma. The review aims to provide pathologists with a practical guide to the implementation and interpretation of PD-L1 testing by immunohistochemistry.

Keywords: Combined positive score; PD-L1; Programmed death ligand-1; immune cell score; immune checkpoint inhibitors; immunohistochemistry; immunotherapy; pathology; predictive biomarker; tumour and immune cell area score; tumour proportion score.

Publication types

  • Review

MeSH terms

  • B7-H1 Antigen / analysis*
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / therapy
  • Carcinoma, Renal Cell / diagnosis
  • Carcinoma, Renal Cell / pathology
  • Carcinoma, Renal Cell / therapy
  • Carcinoma, Transitional Cell / diagnosis
  • Carcinoma, Transitional Cell / pathology
  • Carcinoma, Transitional Cell / therapy
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy
  • Diagnostic Tests, Routine
  • Endometrial Neoplasms / diagnosis
  • Endometrial Neoplasms / pathology
  • Endometrial Neoplasms / therapy
  • Female
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / therapy
  • Humans
  • Immune Checkpoint Inhibitors / analysis
  • Immunohistochemistry
  • Immunotherapy
  • Kidney Neoplasms / diagnosis
  • Kidney Neoplasms / pathology
  • Kidney Neoplasms / therapy
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy
  • Male
  • Melanoma / diagnosis
  • Melanoma / pathology
  • Melanoma / therapy
  • Neoplasm Grading
  • Neoplasms* / diagnosis
  • Neoplasms* / pathology
  • Neoplasms* / therapy
  • Prognosis
  • Programmed Cell Death 1 Receptor / analysis
  • Triple Negative Breast Neoplasms / diagnosis
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy

Substances

  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Immune Checkpoint Inhibitors
  • Programmed Cell Death 1 Receptor