@article{d74aac438d20401480fcd783435388a2,
title = "Integrative genomic analysis reveals low T-cell infiltration as the primary feature of tobacco use in HPV-positive oropharyngeal cancer",
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 = "Genomics, Immunology, Oncology",
author = "Wahle, {Benjamin M.} and Paul Zolkind and Ramirez, {Ricardo J.} and Skidmore, {Zachary L.} and Anderson, {Sydney R.} and Angela Mazul and Hayes, {D. Neil} and Sandulache, {Vlad C.} and Thorstad, {Wade L.} and Douglas Adkins and Griffith, {Obi L.} and Malachi Griffith and Zevallos, {Jose P.}",
note = "Funding Information: Research reported in this publication was supported by National Cancer Institute of the National Institutes of Health under award number R01CA211939-01A1 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: VCS is supported by Career Development Award Number IK2 CX001953 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service.” Funding Information: Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. Funding Information: Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders within the National Institutes of Health, through the “Development of Clinician/Researchers in Academic ENT” training grant, award number T32DC000022 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Funding Information: Research reported in this publication was supported by a Genome Technology Access Center at the McDonnell Genome Institute (GTAC@MGI) Collaboration Pilot grant. Funding for this grant came from GTAC@MGI , the Dean of the School of Medicine, the Department of Arts and Sciences, the Institute of Clinical and Translational Sciences at the Washington University School of Medicine , and Illumina Inc . Funding Information: Research reported in this publication was supported by a Genome Technology Access Center at the McDonnell Genome Institute (GTAC@MGI) Collaboration Pilot grant. Funding for this grant came from GTAC@MGI, the Dean of the School of Medicine, the Department of Arts and Sciences, the Institute of Clinical and Translational Sciences at the Washington University School of Medicine, and Illumina Inc. Research reported in this publication was supported by National Cancer Institute of the National Institutes of Health under award number R01CA211939-01A1. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the National Institute on Deafness and Other Communication Disorders within the National Institutes of Health, through the “Development of Clinician/Researchers in Academic ENT” training grant, award number T32DC000022. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Research reported in this publication was supported by the Washington University Institute of Clinical and Translational Sciences grant UL1TR002345 from the National Center for Advancing Translational Sciences (NCATS) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official view of the NIH. VCS is supported by Career Development Award Number IK2 CX001953 from the United States (U.S.) Department of Veterans Affairs Clinical Sciences R&D (CSRD) Service.”, B.M.W. P.Z. A.M. O.L.G. M.G. and J.P.Z. conceived of and designed the study. A.M. O.L.G. M.G. and J.P.Z. supervised the investigation. B.M.W. P.Z. and R.R. acquired the data. B.M.W. Z.L.S. S.R.A. O.L.G. and M.G. performed the analysis. B.M.W. and P.Z. wrote the manuscript, which was reviewed and edited by R.R. Z.L.S. A.M. D.N.H. V.C.S. W.L.T. D.A. M.G. O.L.G. and J.P.Z. J.P.Z. is a founder and equity shareholder in Droplet Biosciences, an equity shareholder in Summit Biolabs, a consultant for Merck, and receives clinical trial funding from Merck. R.J.R. receives licensing royalties from Washington University for technology licensed to Droplet biosciences. D.A. serves on the advisory boards of Pfizer, Celgene/BMS, Eli Lilly, Merck, and Cue Biopharma. He has received research funding from Aduro, Eli Lilly, Merck, Pfizer, Celgene/BMS, Novartis, Astra Zeneca, Atara Bio, Blueprint Medicine, Celldex, Kura, Exelixis, Innate, Sensei, Matrix BioMed, Hookipa, Co-Factor, Cue Biopharma, Medimmune, and Shanghai Denovo. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = may,
day = "20",
doi = "10.1016/j.isci.2022.104216",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
number = "5",
}