Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma
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Charles R. Schutt1,*, Hua Sun1,2,*, Jaya Sarin Pradhan3, Yvonne Saenger4, Jessica Ley1, Douglas Adkins1,7, Matthew Ingham4, Li Ding1,2,5,7 and Brian A. Van Tine1,6,7
1 Division of Medical Oncology, Washington University in St. Louis, St. Louis, MO, USA
2 McDonnell Genome Institute, Washington University in St. Louis, St. Louis, MO, USA
3 Department of Pathology and Cell Biology, Columbia University, New York, NY, USA
4 Division of Hematology/Oncology, Columbia University, New York, NY, USA
5 Department of Genetics, Washington University in St. Louis, St. Louis, MO, USA
6 Division of Pediatric Hematology and Oncology, St. Louis Children’s Hospital, St. Louis, MO, USA
7 Siteman Cancer Center, St. Louis, MO, USA
* Co-first authors
|Brian A. Van Tine,||email:||[email protected]|
Keywords: head and neck squamous cell carcinoma; neoantigens; mutational evolution; tumor relapse; immune cell infiltration
Abbreviations: ECM: Extracellular Matrix; HNSCC: Head and neck cell squamous-cell carcinomas; HPV: human papilloma virus; IHC: immunohistochemistry; WES: whole exome sequencing
Received: February 02, 2021 Accepted: February 15, 2021 Published: March 16, 2021
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.
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