Immune Landscape of Viral- and Carcinogen-Driven Head and Neck Cancer

Immunity. 2020 Jan 14;52(1):183-199.e9. doi: 10.1016/j.immuni.2019.11.014. Epub 2020 Jan 7.


Head and neck squamous cell carcinoma (HNSCC) arises through exposure to environmental carcinogens or malignant transformation by human papillomavirus (HPV). Here, we assessed the transcriptional profiles of 131,224 single cells from peripheral and intra-tumoral immune populations from patients with HPV- and HPV+ HNSCC and healthy donors. Immune cells within tumors of HPV- and HPV+ HNSCC displayed a spectrum of transcriptional signatures, with helper CD4+ T cells and B cells being relatively divergent and CD8+ T cells and CD4+ regulatory T cells being relatively similar. Transcriptional results were contextualized through multispectral immunofluorescence analyses and evaluating putative cell-cell communication based on spatial proximity. These analyses defined a gene expression signature associated with CD4+ T follicular helper cells that is associated with longer progression-free survival in HNSCC patients. The datasets and analytical approaches herein provide a resource for the further study of the impact of immune cells on viral- and carcinogen-induced cancers.

Keywords: cancer immunology; head and neck cancer; immunotherapy; multispectral immunofluorescence MC; mutagen-driven cancer; single-cell RNAseq; tertiary lymphoid structures; transcriptomics; viral-induced cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alphapapillomavirus / immunology
  • B-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Differentiation / immunology
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / immunology*
  • Head and Neck Neoplasms / virology
  • Humans
  • Immunotherapy
  • Progression-Free Survival
  • Squamous Cell Carcinoma of Head and Neck / genetics
  • Squamous Cell Carcinoma of Head and Neck / immunology*
  • Squamous Cell Carcinoma of Head and Neck / virology
  • T-Lymphocytes, Helper-Inducer / immunology*
  • T-Lymphocytes, Regulatory / immunology*