Immune gene expression in head and neck squamous cell carcinoma patients

Eur J Cancer. 2019 Nov;121:210-223. doi: 10.1016/j.ejca.2019.08.028. Epub 2019 Oct 5.


Background: Nivolumab and pembrolizumab targeting programmed cell death protein 1 (PD-1) have recently been approved among patients with recurrent and/or metastatic head and neck squamous cell carcinoma (HNSCC) who failed platinum therapy. We aimed to evaluate the prognostic value of selected immune gene expression in HNSCC.

Patients and methods: We retrospectively assessed the expression of 46 immune-related genes and immune-cell subpopulation genes including immune checkpoints by real-time polymerase chain reaction among 96 patients with HNSCC who underwent primary surgery at Institut Curie between 1990 and 2006. Univariate and multivariate analyses were performed to assess the prognostic value of dysregulated genes.

Results: The Median age of the population was 56 years [range: 35-78]. Primary tumour location was oral cavity (45%), oropharynx (21%), larynx (18%) and hypopharynx (17%). Twelve patients (13%) had an oropharyngeal human papillomavirus-positive tumour. Most significantly overexpressed immune-related genes were TNFRSF9/4-1BB (77%), IDO1 (75%), TNFSF4/OX40L (74%) and TNFRSF18/GITR (74%), and immune-cell subpopulation gene was FOXP3 (62%). Eighty-five percent of tumours analysed overexpressed actionable immunity genes, including PD-1/PD-L1, TIGIT, OX40/OX40L and/or CTLA4. Among the immune-related genes, high OX40L mRNA level (p = 0.0009) and low PD-1 mRNA level (p = 0.004) were associated with the highest risk of recurrence. Among the immune-cell subpopulation genes, patients with high PDGFRB mRNA level (p < 0.0001) and low CD3E (p = 0.0009) or CD8A mRNA levels (p = 0.004) were also at the highest risk of recurrence.

Conclusions: OX40L and PDGFRB overexpression was associated with poor outcomes, whereas PD-1 overexpression was associated with good prognosis in patients with HNSCC treated with primary surgery, suggesting their relevance as potential prognostic biomarkers and major therapeutic targets.

Keywords: Gene expression; Head and neck squamous cell carcinoma; Immune checkpoints; Prognostic biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • B7-H1 Antigen / genetics
  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / metabolism
  • CD3 Complex / genetics
  • CD8 Antigens / genetics
  • CTLA-4 Antigen / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glucocorticoid-Induced TNFR-Related Protein / genetics
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immune System Phenomena / genetics*
  • Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology
  • OX40 Ligand / genetics
  • Prognosis
  • Programmed Cell Death 1 Receptor / genetics
  • Retrospective Studies
  • Squamous Cell Carcinoma of Head and Neck / diagnosis
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Squamous Cell Carcinoma of Head and Neck / pathology
  • Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics


  • B7-H1 Antigen
  • Biomarkers, Tumor
  • CD274 protein, human
  • CD3 Complex
  • CD3E protein, human
  • CD8 Antigens
  • CD8 antigen, alpha chain
  • CTLA-4 Antigen
  • CTLA4 protein, human
  • Glucocorticoid-Induced TNFR-Related Protein
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • OX40 Ligand
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • TNFRSF18 protein, human
  • TNFRSF9 protein, human
  • TNFSF4 protein, human
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • indoleamine 2,3-dioxygenase 1, human