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Review
. 2023 Feb 1;23(1):15-25.
doi: 10.17305/bjbms.2022.7953.

PD-L1 testing by immunohistochemistry in immuno-oncology

Semir Vranic  1 , Zoran Gatalica  2
Affiliations
Review

PD-L1 testing by immunohistochemistry in immuno-oncology

Semir Vranic et al. Biomol Biomed. .

Abstract

Immunotherapy, based on immune checkpoint inhibitors targeting the Programmed cell death ligand 1 (PD-L1) and/or Programmed Death Receptor 1 (PD-1), has substantially improved the outcomes of patients with various cancers. However, only ~30% of patients benefit from immune checkpoint inhibitors. Tumor PD-L1 expression, assessed by immunohistochemistry, is the most widely validated and used predictive biomarker to guide the selection of patients for immune checkpoint inhibitors. PD-L1 assessment may be challenging due to the necessity for different companion diagnostic assays for required specific immune checkpoint inhibitors and a relatively high level of inter-assay variability in terms of performance and cutoff levels. In this review, we discuss the role of PD-L1 immunohistochemistry as a predictive test in immunotherapy (immuno-oncology), highlight the complexity of the PD-L1 testing landscape, discuss various preanalytical, analytical and clinical issues that are associated with PD-L1 assays, and provide some insights into optimization of PD-L1 as a predictive biomarker in immuno-oncology.

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Figures

Figure 1.
Figure 1.
A morphology (Image A; magnification 40×) of poorly differentiated pulmonary non-small cell lung cancer with a marked nuclear atypia with diffuse and strong membranous PD-L1 expression (Image B; SP142 clone, magnification 20×). PD-L1: Programmed cell death ligand 1.
Figure 2.
Figure 2.
A high-grade triple-negative breast cancer case with metaplastic and pleomorphic features (Image A, magnification 20×) with PD-L1 expression in the tumor-infiltrating lymphocytes (SP142 clone) [, 100]. The tumor cells were devoid of PD-L1 expression (Image B, magnification 20×). PD-L1: Programmed cell death ligand 1.
Figure 3.
Figure 3.
There is an excellent concordance between the four clones in assessing PD-L1 expression in metastatic soft tissue neoplasm (dedifferentiated liposarcoma) (magnification 10×). PD-L1: Programmed cell death ligand 1.
Figure 4.
Figure 4.
A case of diffuse large B-cell lymphoma (DLBCL) exhibiting a discordant expression (in both intensity and percentage) of PD-L1 with the lowest expression with the 22C3 and the highest with SP263 clone (magnification 10×). PD-L1: Programmed cell death ligand 1.
See this image and copyright information in PMC

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