TY - JOUR
T1 - Genomic and neoantigen evolution from primary tumor to first metastases in head and neck squamous cell carcinoma
AU - Schutt, R. R.
AU - Sun, Hua
AU - Pradhan, Jaya Sarin
AU - Saenger, Yvonne
AU - Ley, Jessica
AU - Adkins, Douglas
AU - Ingham, Matthew
AU - Ding, Li
AU - Tine, Brian A.Van
N1 - Publisher Copyright:
© 2021 Impact Journals LLC. All rights reserved.
PY - 2021/3/1
Y1 - 2021/3/1
N2 - 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.
AB - 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.
KW - Head And Neck Squamous Cell Carcinoma
KW - Immune Cell Infiltration
KW - Mutational Evolution
KW - Neoantigens
KW - Tumor Relapse
UR - http://www.scopus.com/inward/record.url?scp=85104404835&partnerID=8YFLogxK
U2 - 10.18632/ONCOTARGET.27907
DO - 10.18632/ONCOTARGET.27907
M3 - Article
C2 - 33796222
AN - SCOPUS:85104404835
SN - 1949-2553
VL - 12
SP - 534
EP - 548
JO - Oncotarget
JF - Oncotarget
IS - 6
ER -