A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer - Archive ouverte HAL Access content directly
Journal Articles Frontiers in Immunology Year : 2023

A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer

Christelle Lony
  • Function : Author
Anaïs Nicol
  • Function : Author
  • PersonId : 1347483
Patrick Roncarati
  • Function : Author
Mickaël Burgy
  • Function : Author
  • PersonId : 1347488
Michaël Herfs
  • Function : Author

Abstract

BACKGROUND: Deconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments. METHODS: Transcriptomic data from HPV-positive OSCC samples were analyzed using unsupervised hierarchical clustering, and clinical relevance was evaluated using Kaplan-Meier analysis. HPV-positive OSCC cell line models were used in functional analyses and phenotypic assays to assess cell migration and invasion, response to cisplatin, and phagocytosis by macrophages in vitro. RESULTS: We found, by transcriptomic analysis of HPV-positive OSCC samples, a ΔNp63 dependent molecular signature that is associated with patient prognosis. ΔNp63 was found to act as a tumor suppressor in HPV-positive OSCC at multiple levels. It inhibits cell migration and invasion, and favors response to chemotherapy. RNA-Seq analysis uncovered an unexpected regulation of genes, such as DKK3, which are involved in immune response-signalling pathways. In agreement with these observations, we found that ΔNp63 expression levels correlate with an enhanced anti-tumor immune environment in OSCC, and ΔNp63 promotes cancer cell phagocytosis by macrophages through a DKK3/NF-κB-dependent pathway. CONCLUSION: Our findings are the first comprehensive identification of molecular mechanisms involved in the heterogeneous prognosis of HPV-positive OSCC, paving the way for much-needed biomarkers and targeted treatment.

Domains

Immunology
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Origin : Publication funded by an institution
Licence : CC BY - Attribution

Dates and versions

hal-04440322 , version 1 (06-02-2024)

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Jana Mourtada, Christelle Lony, Anaïs Nicol, Justine de Azevedo, Cyril Bour, et al.. A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer. Frontiers in Immunology, 2023, 14, pp.1264093. ⟨10.3389/fimmu.2023.1264093⟩. ⟨hal-04440322⟩
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