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 - Funding Information:
Charles Schutt: No disclosures, Hua Sun: No disclosures, Jaya Sarin: No disclosures, Dr. Adkins: Consulting or scientific advisory board support from Pfizer, Merck, Eli Lilly, Celgene (now BMS), Cue Biopharma. Institutional research support from Pfizer Eli Lilly, Merck, Celgene/BMS, Novartis, AstraZeneca, Atara Bio, Blueprint Medicine, Celldex, Enzychem, Kura, Exelixis, Innate, Sensei, and Matrix Biomed. Yvonne Saenger: Research funding from Amgen and Regeneron. Equity on a biomarker startup, Wasaba. Jessica Ley: No disclosures. Matthew Ingham: Consulting or Advisory role: Daiichi Sanky; Research Funding: Mirati Therapeutics, Apexigen, PTC Therapeutics; Travel, Accommodations, Expenses: Genetech, Mirati Therapeutics. Li Ding: No disclosures. Brian Van Tine: Grants from Merck, grants and personal fees from Pfizer, grants from Tracon, grants, personal fees and other from GSK, personal fees from Polaris, personal fees from Lilly, personal fees from Caris Life Sciences, personal fees from Novartis, personal fees from CytRX, personal fees from Plexxikon, personal fees from Epizyme, personal fees from Daiihi Sankyo, personal fees from Adaptimmune, personal fees from Immune Design, personal fees from Bayer, personal fees from Cytokinetics, personal fees from Deciphera. In addition, Dr. Van Tine has a patent on the use of ME1 as biomarker and ALEXT3102 issued.
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 -