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

Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors
Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors
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.
head and neck squamous cell carcinoma, human papilloma virus, tumor-infiltrating lymphocyte, RNA-Sequencing, transcriptome
1949-2553
1-17
Wood, Oliver
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Woo, Jeongmin
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Seumois, Gregory
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Savelyeva, Natalia
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Mccann, Katy J.
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Singh, Divya
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Jones, Terry
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Peel, Lailah
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Breen, Michael S
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Ward, Matthew
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Garrido Martin, Eva
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Sanchez-Elsner, Tilman
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Thomas, Gareth
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Vijayanand, Pandurangan
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Woelk, Christopher H.
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King, Emma
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Ottensmeier, Christian
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Wood, Oliver
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Woo, Jeongmin
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Seumois, Gregory
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Savelyeva, Natalia
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Mccann, Katy J.
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Singh, Divya
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Jones, Terry
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Peel, Lailah
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Breen, Michael S
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Ward, Matthew
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Garrido Martin, Eva
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Sanchez-Elsner, Tilman
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Thomas, Gareth
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Vijayanand, Pandurangan
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Woelk, Christopher H.
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King, Emma
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Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797

Wood, Oliver, Woo, Jeongmin, Seumois, Gregory, Savelyeva, Natalia, Mccann, Katy J., Singh, Divya, Jones, Terry, Peel, Lailah, Breen, Michael S, Ward, Matthew, Garrido Martin, Eva, Sanchez-Elsner, Tilman, Thomas, Gareth, Vijayanand, Pandurangan, Woelk, Christopher H., King, Emma and Ottensmeier, Christian (2016) Gene expression analysis of TIL rich HPV-driven head and neck tumors reveals a distinct B-cell signature when compared to HPV independent tumors. Oncotarget, 1-17. (doi:10.18632/oncotarget.10788). (PMID:27462861)

Record type: Article

Abstract

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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Accepted/In Press date: 30 June 2016
e-pub ahead of print date: 22 July 2016
Published date: 22 July 2016
Keywords: head and neck squamous cell carcinoma, human papilloma virus, tumor-infiltrating lymphocyte, RNA-Sequencing, transcriptome
Organisations: Cancer Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 398747
URI: https://eprints.soton.ac.uk/id/eprint/398747
ISSN: 1949-2553
PURE UUID: 6cee2613-680a-4b57-8fc2-15539bc41de5

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Date deposited: 02 Aug 2016 08:32
Last modified: 09 Dec 2019 19:31

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