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

• Main Authors: Attignon, V. (Author), Auclair-Perossier, J. (Author), Benzerdjeb, N. (Author), Bouaoud, J. (Author), Crozes, C. (Author), Fayette, J. (Author), Gadot, N. (Author), Kamal, M. (Author), Karabajakian, A. (Author), Le Tourneau, C. (Author), Michon, L. (Author), Saintigny, P. (Author), Zrounba, P. (Author)
• Format: Article
• Language: English
• Published: Elsevier Ltd 2021
• Subjects: adult; advanced cancer; aged; antineoplastic agent; Article; B7-H1 Antigen; cancer recurrence; cancer surgery; cetuximab; clinical article; controlled study; female; follow up; gamma interferon; gene expression; Gene expression; gene expression profiling; genetics; Head and Neck Neoplasms; head and neck squamous cell carcinoma; head and neck tumor; human; human tissue; Humans; immunohistochemistry; male; messenger RNA; neck dissection; neoadjuvant chemotherapy; Neoplasm Recurrence, Local; nuclease protection assay; polymerase chain reaction; programmed death 1 ligand 1; Programmed Death Ligand 1; protein expression; protein expression level; protein p16; RNA sequencing; Squamous Cell Carcinoma of Head and Neck; systemic therapy; tertiary lymphoid structure; transcriptome; Transcriptome; tumor recurrence
• Online Access: View Fulltext in Publisher
• ISBN: 13688375 (ISSN)
• DOI: 10.1016/j.oraloncology.2021.105368

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. © 2021 The Author(s)