Comprehensive characterization of the tumor microenvironment for assessing immunotherapy outcome in patients with head and neck squamous cell carcinoma

Aging (Albany NY). 2020 Nov 18;12(22):22509-22526. doi: 10.18632/aging.103460. Epub 2020 Nov 18.

Abstract

The tumor microenvironment (TME) constitutes a complex milieu of cells and cytokines that maintain equilibrium between tumor progression and prognosis. However, comprehensive analysis of the TME and its clinical significance in head and neck squamous cell carcinoma (HNSCC) remains to be unreported. In this study, based on large-scale RNA sequencing data pertaining to single nucleotide variants (SNVs) and copy number variations (CNVs) in HNSCC patients from The Cancer Genome Atlas database, we analysed subpopulations of infiltrating immune cells and evaluated the role of TME infiltration pattern (TME score) in assessing immunotherapy outcome. TME signature genes involved in several inflammation and immunity signalling pathways were observed in the TME score subtype, which were considered immunosuppressive and potentially responsible for significantly worse prognosis. In comparison with SNV- and CNV-mediated tumor mutation burden, TME score can significantly differentiate between high- and low-risk HNSCC and predict immunotherapy outcome. Our data provide clarity on the comprehensive landscape of interactions between clinical characteristics of HNSCC and tumor-infiltrating immune cells. TME score seems to be a useful biomarker that can predict immunotherapy outcome in HNSCC patients.

Keywords: copy number variations; head and neck squamous cell carcinoma; immunotherapy; single nucleotide variants; tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Databases, Genetic
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Regulatory Networks
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology
  • Head and Neck Neoplasms / therapy*
  • Humans
  • Immunotherapy*
  • Mutation
  • Predictive Value of Tests
  • RNA-Seq
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology
  • Squamous Cell Carcinoma of Head and Neck / therapy*
  • Transcriptome
  • Treatment Outcome
  • Tumor Microenvironment*

Substances

  • Biomarkers, Tumor