Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma

R. R. Schutt, Hua Sun, Jaya Sarin Pradhan, Yvonne Saenger, Jessica Ley, Douglas Adkins, Matthew Ingham, Li Ding, Brian A.Van Tine

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Head and neck cell squamous-cell carcinomas (HNSCC) are a group of common cancers typically associated with tobacco use and human papilloma virus infection. Up to half of all cases will suffer a recurrence after primary treatment. As such, new therapies are needed, including therapies which promote the anti-tumor immune response. Prior work has characterized changes in the mutation burden between primary and recurrent tumors; however, little work has characterized the changes in neoantigen evolution. We characterized genomic and neoantigen changes between 23 paired primary and recurrent HNSCC tumors. Twenty-three biopsies from patients originally diagnosed with locally advanced disease were identified from the Washington University tumor bank. Whole exosome sequencing, RNA-seq, and immunohistochemistry was performed on the primary and recurrent tumors. Within these tumors, we identified 6 genes which have predicted neoantigens in 4 or more patients. Interestingly, patients with neoantigens in these shared genes had increased CD3+ CD8+ T cell infiltration and duration of survival with disease. Within HNSCC tumors examined here, there are neoantigens in shared genes by a subset of patients. The presence of neoantigens in these shared genes may promote an anti-tumor immune response which controls tumor progression.

Original languageEnglish
Pages (from-to)534-548
Number of pages15
JournalOncotarget
Volume12
Issue number6
DOIs
StatePublished - Mar 1 2021

Keywords

  • Head And Neck Squamous Cell Carcinoma
  • Immune Cell Infiltration
  • Mutational Evolution
  • Neoantigens
  • Tumor Relapse

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