Abstract
Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far.Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering.Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies.Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones.
Highlights
In a growing number of solid tumors, immunotherapy by checkpoint blockage targeting programmed death receptor 1 (PD-1) or its ligand programmed death-ligand 1 (PD-L1) has become a standard treatment [1,2,3,4,5,6,7,8,9]
Our cohort is well-representative for head and neck squamous cell carcinomas (HNSCC) and well-reflects the aggressive tumor behavior [19]
For HNSCC, survival improved compared to the previous standard of care
Summary
In a growing number of solid tumors, immunotherapy by checkpoint blockage targeting programmed death receptor 1 (PD-1) or its ligand programmed death-ligand 1 (PD-L1) has become a standard treatment [1,2,3,4,5,6,7,8,9]. The response to the administration of most PD-1 or PD-L1 inhibitors often correlates with PD-L1 expression determined before therapy using specific companion diagnostics for immunohistochemistry (IHC) resulting in approval in combination with PD-L1 expression as a diagnostic biomarker [8, 9]. While IHC is a routine tool in modern pathology to investigate diagnostic and predictive markers in tissue samples, its use in PD-L1 expression analysis has raised several issues: (a) There are different PD-L1 assays each specific to a therapeutic antibody without a common standard. The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far
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