Oncotarget

Research Papers:

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

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

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Oncotarget. 2021; 12:534-548. https://doi.org/10.18632/oncotarget.27907

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Abstract

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

Correspondence to:

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

Copyright: © 2021 Schutt et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.


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