Development of a Prototype Immunohistochemistry Assay to Measure Programmed Death Ligand-1 Expression in Tumor Tissue

Arch Pathol Lab Med. 2016 Nov;140(11):1259-1266. doi: 10.5858/arpa.2015-0544-OA.

Abstract

Context: - With the abundance of therapeutics targeted against programmed death receptor-1 and its ligand (PD-L1) that are currently approved or in clinical development, there is interest in identifying those patients most likely to respond to these drugs. Expression of PD-L1 may be an indicator of an initial and robust inflammatory response to the presence of tumor cells. Therefore, tumors that express PD-L1 may be the most likely to respond to therapies that interrupt the negative feedback mechanism that leads to PD-L1 upregulation.

Objective: - To develop a prototype immunohistochemistry assay using the anti-PD-L1 antibody clone 22C3.

Design: - The assay was developed and optimized using commercially available reagents and archival tumor-bank tissue.

Results: - The optimized immunohistochemistry method had high precision and reproducibility. Using the prototype assay in 142 non-small cell lung cancer and 79 melanoma archival tumor-bank tissue samples, PD-L1 staining was observed at the plasma membrane of nucleated tumor and nontumor cells and, in some cases, as a distinct lichenoid pattern at the tumor-stroma border. Using a preliminary scoring method, 56% (80 of 142) of non-small cell lung cancer and 53% (42 of 79) of melanoma samples were defined as PD-L1+ based on a modified H-score of 1 or more or the presence of a distinctive staining pattern at the tumor-stroma interface.

Conclusions: - The immunohistochemistry assay using the anti-PD-L1 antibody 22C3 merits further investigation in clinical trials and prevalence assessments to further understand the prognostic and predictive value of PD-L1 expression in cancer.

Publication types

  • Comparative Study
  • Validation Study

MeSH terms

  • Animals
  • Antibodies, Monoclonal / metabolism*
  • Antibody Specificity
  • B7-H1 Antigen / antagonists & inhibitors
  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism*
  • Biomarkers, Tumor / metabolism
  • CHO Cells
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Membrane / metabolism
  • Cell Membrane / pathology
  • Clone Cells
  • Cricetulus
  • Humans
  • Immunohistochemistry
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Melanoma / diagnosis
  • Melanoma / metabolism*
  • Melanoma / pathology
  • Mice
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tissue Banks

Substances

  • Antibodies, Monoclonal
  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • Neoplasm Proteins
  • Recombinant Proteins