Immune gene expression in head and neck squamous cell carcinoma patients.

Adult Aged B7-H1 Antigen / genetics Biomarkers, Tumor / genetics 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 Humans Immune System Phenomena / genetics Indoleamine-Pyrrole 2,3,-Dioxygenase / genetics Male Middle Aged Neoplasm Recurrence, Local / diagnosis OX40 Ligand / genetics Prognosis Programmed Cell Death 1 Receptor / genetics Retrospective Studies Squamous Cell Carcinoma of Head and Neck / diagnosis Tumor Necrosis Factor Receptor Superfamily, Member 9 / genetics

Gene expression Head and neck squamous cell carcinoma Immune checkpoints Prognostic biomarker

Journal

European journal of cancer (Oxford, England : 1990)

ISSN: 1879-0852

Titre abrégé: Eur J Cancer

Pays: England

ID NLM: 9005373

Informations de publication

Date de publication:
11 2019

Historique:

received: 06 02 2019

revised: 03 07 2019

accepted: 30 08 2019

pubmed: 9 10 2019

medline: 9 6 2020

entrez: 9 10 2019

Statut: ppublish

Résumé

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. 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. 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. 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.

Sections du résumé

BACKGROUND

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.

Identifiants

DOI: 10.1016/j.ejca.2019.08.028 PMID: 31593831

pubmed: 31593831

pii: S0959-8049(19)30488-5

doi: 10.1016/j.ejca.2019.08.028

pii:

doi:

Substances chimiques

B7-H1 Antigen 0

Biomarkers, Tumor 0

CD274 protein, human 0

CD3 Complex 0

CD3E protein, human 0

CD8 Antigens 0

CD8 antigen, alpha chain 0

CTLA-4 Antigen 0

CTLA4 protein, human 0

Glucocorticoid-Induced TNFR-Related Protein 0

IDO1 protein, human 0

Indoleamine-Pyrrole 2,3,-Dioxygenase 0

OX40 Ligand 0

PDCD1 protein, human 0

Programmed Cell Death 1 Receptor 0

TNFRSF18 protein, human 0

TNFRSF9 protein, human 0

TNFSF4 protein, human 0

Tumor Necrosis Factor Receptor Superfamily, Member 9 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

Pagination

210-223