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Updated: Nov 10, 2025
Therapy Testing in a Spheroid-based 3D Cell Culture Model for Head and Neck Squamous Cell Carcinoma
Published on: April 20, 2018
Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma
Charles R Schutt1,2, Hua Sun1,3,2, Jaya Sarin Pradhan4
1Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA.
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.
Insights
Investigating head and neck squamous cell carcinomas (HNSCC), this study reveals shared neoantigens in recurrent tumors. These neoantigens correlate with increased T cell infiltration and improved survival, suggesting a potential therapeutic target.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Head and neck squamous cell carcinomas (HNSCC) frequently recur after primary treatment.
- Understanding neoantigen evolution in recurrent HNSCC is crucial for developing novel immunotherapies.
- Existing research has focused on mutation burden, with less attention to neoantigenic changes.
Purpose of the Study:
- To characterize genomic and neoantigen alterations between paired primary and recurrent HNSCC tumors.
- To investigate the association between shared neoantigens and anti-tumor immune responses.
- To explore the impact of neoantigen evolution on patient survival.
Main Methods:
- Analysis of 23 paired primary and recurrent HNSCC tumor biopsies.
- Whole exome sequencing and RNA-sequencing.
- Immunohistochemistry to assess T cell infiltration (CD3+ CD8+).
Main Results:
- Identified 6 genes with predicted neoantigens in at least 4 patients across the cohort.
- Patients with neoantigens in these shared genes exhibited increased CD3+ CD8+ T cell infiltration.
- A positive correlation was observed between shared neoantigens and longer duration of survival with disease.
Conclusions:
- Shared neoantigens are present in a subset of recurrent HNSCC tumors.
- The presence of these neoantigens may stimulate an anti-tumor immune response.
- Targeting shared neoantigens could represent a promising strategy for HNSCC treatment.
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