Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Julika Ribbat-Idel*, Franz F. Dressler, Rosemarie Krupar, Christian Watermann, Finn Ole Paulsen, Patrick Kuppler, Luise Klapper, Anne Offermann, Barbara Wollenberg, Dirk Rades, Simon Laban, Markus Reischl, Karl Ludwig Bruchhage, Christian Idel, Sven Perner

*Corresponding author for this work


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.

Original languageEnglish
Article number640515
JournalFrontiers in medicine
Pages (from-to)640515
Publication statusPublished - 27.04.2021


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