Language
English
Publication Date
5-20-2022
Journal
iScience
DOI
10.1016/j.isci.2022.104216
PMID
35494251
PMCID
PMC9044176
PubMedCentral® Posted Date
4-6-2022
PubMedCentral® Full Text Version
Post-print
Abstract
Although tobacco use is an independent adverse prognostic feature in HPV(+) oropharyngeal squamous cell carcinoma (OPSCC), the biologic features associated with tobacco use have not been systematically investigated. We characterized genomic and immunologic features associated with tobacco use through whole exome sequencing, mRNA hybridization, and immunohistochemical staining in 47 HPV(+) OPSCC tumors. Low expression of transcripts in a T cell-inflamed gene expression profile (TGEP) was associated with tobacco use at diagnosis and lower overall and disease-free survival. Tobacco use was associated with an increased proportion of T > C substitutions and a lower proportion of expected mutational signatures, but not with increases in mutational burden or recurrent oncogenic mutations. Our findings suggest that rather than increased mutational burden, tobacco's primary and clinically relevant association in HPV(+) OPSCC is immunosuppression of the tumor immune microenvironment. Quantitative assays of T cell infiltration merit further study as prognostic markers in HPV(+) OPSCC.
Keywords
Oncology, Immunology, Genomics
Published Open-Access
yes
Recommended Citation
Wahle, Benjamin M; Zolkind, Paul; Ramirez, Ricardo J; et al., "Integrative Genomic Analysis Reveals Low T-Cell Infiltration As the Primary Feature of Tobacco Use in HPV-Positive Oropharyngeal Cancer" (2022). Faculty and Staff Publications. 2818.
https://digitalcommons.library.tmc.edu/baylor_docs/2818
Graphical Abstract
Included in
Immunology and Infectious Disease Commons, Medical Sciences Commons, Oncology Commons, Otolaryngology Commons, Otorhinolaryngologic Diseases Commons