Longitudinal assessment of PD-L1 expression and gene expression profiles in patients with head and neck cancer reveals temporal heterogeneity - Bio-informatique (CBIO) Access content directly
Journal Articles Oral Oncology Year : 2021

Longitudinal assessment of PD-L1 expression and gene expression profiles in patients with head and neck cancer reveals temporal heterogeneity

Abstract

Background: Programmed death-ligand 1 (PD-L1) is the most validated predictive biomarker used for the treatment of head and neck squamous cell carcinoma (HNSCC) with immune checkpoint inhibitors (ICI). Several gene expression-based signatures surrogate of the activation of IFN-gamma pathway and of the presence of tertiary lymphoid structures (TLS) have also been proposed as potential biomarkers. While they may have a potential therapeutic implication, the longitudinal changes of either PD-L1 or gene expression profiles between the initial and recurrent HNSCC lesions is unknown. Methods: PD-L1 immunohistochemistry (IHC) and targeted RNA-sequencing of 2,549 transcripts were analyzed on paired specimens from the initial diagnosis and recurrent HNSCC. PD-L1 status was defined using the combined positive score (CPS). PD-L1 mRNA levels were compared with protein expression levels by IHC. Enrichment scores of surrogate signatures for TLS and IFN-gamma (IFN-γ) pathway activation were computed using the single sample gene set enrichment analysis (ssGSEA). Results: PD-L1 status was 64% (21/33) concordant between the initial and recurrent lesions using a CPS 1 threshold and 67% (22/33) concordant using a CPS 20 threshold. CPS score was associated with PD-L1 gene expression levels. There was a 43% (15/35) and 66% (23/35) concordance for the IFN-γ and TLS signature scores, respectively. Conclusion: Our study reveals temporal heterogeneity of PD-L1 status and TLS/IFN-γ gene expression surrogates in HNSCC that need to be considered when interpreting biomarker studies.
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hal-03865051 , version 1 (13-06-2023)

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Attribution - NonCommercial

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Andy Karabajakian, Jebrane Bouaoud, Lucas Michon, Maud Kamal, Carole Crozes, et al.. Longitudinal assessment of PD-L1 expression and gene expression profiles in patients with head and neck cancer reveals temporal heterogeneity. Oral Oncology, 2021, 119, pp.105368. ⟨10.1016/j.oraloncology.2021.105368⟩. ⟨hal-03865051⟩
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