The University of Southampton
University of Southampton Institutional Repository

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
56781-56797
Wood, Oliver
b9b57016-5f60-466c-983f-38958426c4b5
Woo, Jeongmin
f31ed6e0-741c-4ccf-8e14-3b4f92bac2b7
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Mccann, Katy J.
154f6b6d-c8b2-43b2-a8a9-ffe243da40c6
Singh, Divya
ec02f7f5-fa4a-4dde-a838-eb9adf8e9210
Jones, Terry
9d84f271-9bda-4a23-98a3-8a442f457d97
Peel, Lailah
0980984d-3cd1-4fd7-accf-0ebad0912091
Breen, Michael S
4754f7c6-127d-42e9-9d0e-8c4ef6272ac9
Ward, Matthew
70aa3196-7f98-49ea-876b-38f2b6364d72
Garrido Martin, Eva
bba99077-0684-4516-8a15-e80409c12734
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
King, Emma
d85e0e8f-7295-4912-9052-646a790d99db
Ottensmeier, Christian
42b8a398-baac-4843-a3d6-056225675797
Wood, Oliver
b9b57016-5f60-466c-983f-38958426c4b5
Woo, Jeongmin
f31ed6e0-741c-4ccf-8e14-3b4f92bac2b7
Seumois, Gregory
0be7d3d6-5526-458c-aa5c-cce52410a2ed
Savelyeva, Natalia
804c3e15-d260-4717-9b7c-15c16ba87fc7
Mccann, Katy J.
154f6b6d-c8b2-43b2-a8a9-ffe243da40c6
Singh, Divya
ec02f7f5-fa4a-4dde-a838-eb9adf8e9210
Jones, Terry
9d84f271-9bda-4a23-98a3-8a442f457d97
Peel, Lailah
0980984d-3cd1-4fd7-accf-0ebad0912091
Breen, Michael S
4754f7c6-127d-42e9-9d0e-8c4ef6272ac9
Ward, Matthew
70aa3196-7f98-49ea-876b-38f2b6364d72
Garrido Martin, Eva
bba99077-0684-4516-8a15-e80409c12734
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Thomas, Gareth
2ff54aa9-a766-416b-91ee-cf1c5be74106
Vijayanand, Pandurangan
79514f33-66cf-47cc-a8fa-46bbfc21b7d1
Woelk, Christopher H.
4d3af0fd-658f-4626-b3b5-49a6192bcf7d
King, Emma
d85e0e8f-7295-4912-9052-646a790d99db
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, 7 (35), 56781-56797. (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.

Text
Final HNSCC manuscript Onct.docx - Accepted Manuscript
Available under License Other.
Download (240kB)
Text
Final Figures Onct.pdf - Accepted Manuscript
Available under License Other.
Download (1MB)
Text
10788-163854-2-PB.pdf - Version of Record
Available under License Other.
Download (4MB)
Text
Final Supplementary Methods Onct.docx - Other
Available under License Other.
Download (61kB)
Spreadsheet
Copy of Final Supplementary tables S1-11.xlsx - Other
Available under License Other.
Download (322kB)
Text
Final Supplementary Figures Onct.pdf - Other
Available under License Other.
Download (1MB)

Show all 6 downloads.

More information

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: http://eprints.soton.ac.uk/id/eprint/398747
ISSN: 1949-2553
PURE UUID: 6cee2613-680a-4b57-8fc2-15539bc41de5
ORCID for Tilman Sanchez-Elsner: ORCID iD orcid.org/0000-0003-1915-2410
ORCID for Pandurangan Vijayanand: ORCID iD orcid.org/0000-0001-7067-9723

Catalogue record

Date deposited: 02 Aug 2016 08:32
Last modified: 15 Mar 2024 03:29

Export record

Altmetrics

Contributors

Author: Oliver Wood
Author: Jeongmin Woo
Author: Gregory Seumois
Author: Katy J. Mccann
Author: Divya Singh
Author: Terry Jones
Author: Lailah Peel
Author: Michael S Breen
Author: Matthew Ward
Author: Eva Garrido Martin
Author: Gareth Thomas
Author: Pandurangan Vijayanand ORCID iD
Author: Christopher H. Woelk
Author: Emma King

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×