Longitudinal assessment of PD-L1 expression and gene expression profiles in patients with head and neck cancer reveals temporal heterogeneity. (August 2021)

• Record Type: Journal Article
• Authors: Karabajakian, Andy; Bouaoud, Jebrane; Michon, Lucas; Kamal, Maud; Crozes, Carole; Zrounba, Philippe; Auclair-Perossier, Jessie; Gadot, Nicolas; Attignon, Valéry; Le Tourneau, Christophe; Benzerdjeb, Nazim; Fayette, Jérôme; Saintigny, Pierre
• Is Part Of: Oral oncology. Volume 119(2021)
• Publication Date: 2021-08
• Subjects: Programmed Death Ligand 1 -- Transcriptome -- Squamous Cell Carcinoma of Head and Neck -- Gene expression; APC antigen-presenting cells -- CPS combined positive score -- CTLA4 cytotoxic T-lymphocyte antigen 4 -- FFPE formalin-fixed, paraffin-embedded -- GEP gene expression profiles -- GSEA gene set enrichment analysis -- HNSCC head & neck squamous cell carcinoma -- HPV human-papillomavirus -- ICI immune checkpoint inhibitors -- IFN-γ interferon-gamma -- KIR killer immunoglobulin-like receptor -- OS overall survival -- OSCC oral squamous cell carcinoma -- PD-L1 programmed death-ligand 1 -- PFS progression-free survival -- RECIST Response Evaluation Criteria in Solid Tumors -- R/M recurrent/metastatic -- ssGSEA single sample gene set enrichment analysis -- SS surgical specimens -- TB tumor biopsy -- TLS tertiary lymphoid structures; Mouth -- Cancer -- Periodicals; Mouth -- Tumors -- Periodicals; Mouth Diseases -- Periodicals; Mouth Neoplasms -- Periodicals; Bouche -- Cancer -- Périodiques; Bouche -- Tumeurs -- Périodiques; Tumeurs -- Périodiques; Electronic journals; 616.9943105
• DOI: 10.1016/j.oraloncology.2021.105368
• Languages: English
• ISSNs: 1368-8375

Abstract

Highlights: PD-L1 expression and gene expression profiles were longitudinally assessed. PD-L1 status was 64% to 70% concordant depending on the CPS threshold. There was a 43% concordance for the IFN-signature score. There was a 66% concordance for the TLS signature score. CPS score was associated with PD-L1 gene expression levels. 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.