Research Papers:

Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors

Oliver Wood, Jeongmin Woo, Gregory Seumois, Natalia Savelyeva, Katy J. McCann, Divya Singh, Terry Jones, Lailah Peel, Michael S. Breen, Matthew Ward, Eva Garrido Martin, Tilman Sanchez-Elsner, Gareth Thomas, Pandurangan Vijayanand, Christopher H. Woelk, Emma King _ and Christian Ottensmeier

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Oncotarget. 2016; 7:56781-56797. https://doi.org/10.18632/oncotarget.10788

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Oliver Wood1,*, Jeongmin Woo1,*, Gregory Seumois3,*, Natalia Savelyeva1, Katy J. McCann1, Divya Singh3, Terry Jones2, Lailah Peel1, Michael S. Breen1, Matthew Ward1, Eva Garrido Martin1, Tilman Sanchez-Elsner1,#, Gareth Thomas1,#, Pandurangan Vijayanand1,3,#, Christopher H. Woelk1,#, Emma King1,#, Christian Ottensmeier1,#, for the SPARC Consortium

1Faculty of Medicine, University of Southampton & University Hospital Southampton, Southampton, UK

2Department of Molecular and Clinical Cancer Medicine, University of Liverpool, Liverpool, UK

3La Jolla Institute for Allergy & Immunology, La Jolla, CA, USA

*These first authors have contributed equally to this work

#These senior authors have contributed equally to this work

Correspondence to:

Emma King, email: e.king@soton.ac.uk

Christopher H. Woelk, email: C.H.Woelk@soton.ac.uk

Keywords: head and neck squamous cell carcinoma, human papilloma virus, tumor-infiltrating lymphocyte, RNA-Sequencing, transcriptome

Received: February 15, 2016    Accepted: June 30, 2016    Published: July 22, 2016


Human papilloma virus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) has a better prognosis than it’s HPV negative (HPV(−)) counterpart. This may be due to the higher numbers of tumor-infiltrating lymphocytes (TILs) in HPV positive (HPV(+)) tumors. RNA-Sequencing (RNA-Seq) was used to evaluate whether the differences in clinical behaviour simply reflect a numerical difference in TILs or whether there is a fundamental behavioural difference between TILs in these two settings. Thirty-nine HNSCC tumors were scored for TIL density by immunohistochemistry. After the removal of 16 TILlow tumors, RNA-Seq analysis was performed on 23 TILhigh/med tumors (HPV(+) n=10 and HPV(−) n=13). Using EdgeR, differentially expressed genes (DEG) were identified. Immune subset analysis was performed using Functional Analysis of Individual RNA-Seq/ Microarray Expression (FAIME) and immune gene RNA transcript count analysis. In total, 1,634 DEGs were identified, with a dominant immune signature observed in HPV(+) tumors. After normalizing the expression profiles to account for differences in B- and T-cell number, 437 significantly DEGs remained. A B-cell associated signature distinguished HPV(+) from HPV(−) tumors, and included the DEGs CD200, GGA2, ADAM28, STAG3, SPIB, VCAM1, BCL2 and ICOSLG; the immune signal relative to T-cells was qualitatively similar between TILs of both tumor cohorts. Our findings were validated and confirmed in two independent cohorts using TCGA data and tumor-infiltrating B-cells from additional HPV(+) HNSCC patients. A B-cell associated signal segregated tumors relative to HPV status. Our data suggests that the role of B-cells in the adaptive immune response to HPV(+) HNSCC requires re-assessment.

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