Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Xu Peng; Isaac Woodhouse; Gemma Hancock; Robert Parker; Kristina Marx; Julius Müller; Silvia Salatino; Thomas Partridge; Annalisa Nicastri; Hanqing Liao; Gary Kruppa; Karin Hellner; Lucy Dorrell; Nicola Ternette

doi:10.1016/j.isci.2023.106101

Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Xu Peng
, Isaac Woodhouse
, Gemma Hancock
, Robert Parker
, Kristina Marx
, Julius Müller
, Silvia Salatino
, Thomas Partridge
, Annalisa Nicastri
, Hanqing Liao
, Gary Kruppa
, Karin Hellner
, Lucy Dorrell
, Nicola Ternette^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Current immunotherapeutic approaches for human papillomavirus (HPV)-driven cervical cancer target the viral oncogenes E6 and E7. We report viral canonical and alternative reading frame (ARF)-derived sequences presented on cervical tumor cells, including antigens encoded by the conserved viral gene E1. We confirm immunogenicity of the identified viral peptides in HPV-positive women, and women with cervical intraepithelial neoplasia. We observe consistent transcription of the E1, E6, and E7 genes in 10 primary cervical tumor resections from the four most common high-risk HPV subtypes (HPV16, 18, 31, and 45), suggesting the suitability of E1 as therapeutic target. We finally confirm HLA presentation of canonical peptides derived from E6 and E7, and ARF-derived viral peptides from a reverse-strand transcript spanning the HPV E1 and E2 genes in primary human cervical tumor tissue. Our results extend currently known viral immunotherapeutic targets in cervical cancer and highlight E1 as an important cervical cancer antigen.

Original language	English
Article number	106101
Number of pages	18
Journal	iScience
Volume	26
Issue number	3
DOIs	https://doi.org/10.1016/j.isci.2023.106101
Publication status	Published - 17 Mar 2023

Bibliographical note

Publisher Copyright:
© 2023 The Author(s)

Funding

This work was funded by a Cancer Research UK Cancer Immunology project award C55884/A21045 and Cancer Research UK RadNet Center Award C6078/A28736 . We thank the Oxford Genomics Center at the Wellcome Center for Human Genetics for the generation and initial processing of the sequencing data. The research was supported by the Wellcome Trust Core Award Grant Number 203141/Z/16/Z with additional support from the NIHR Oxford BRC . The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health. Mass spectrometry acquisition was performed by X.P. and N.T. in the TDI MS Laboratory (University of Oxford) led by Prof. Benedikt M. Kessler.

Funders	Funder number
Netherlands Cancer Institute	C55884/A21045
Cancer Research UK RadNet Center	C6078/A28736
Wellcome Trust	203141/Z/16/Z
National Institute for Health and Care Research

Keywords

Cancer
Cell biology
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.isci.2023.106101Licence: CC BY

PIIS2589004223001785Final published version, 2.39 MBLicence: CC BY

Cite this

Peng, X., Woodhouse, I., Hancock, G., Parker, R., Marx, K., Müller, J., Salatino, S., Partridge, T., Nicastri, A., Liao, H., Kruppa, G., Hellner, K., Dorrell, L., & Ternette, N. (2023). Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer. iScience, 26(3), Article 106101. https://doi.org/10.1016/j.isci.2023.106101

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abstract = "Current immunotherapeutic approaches for human papillomavirus (HPV)-driven cervical cancer target the viral oncogenes E6 and E7. We report viral canonical and alternative reading frame (ARF)-derived sequences presented on cervical tumor cells, including antigens encoded by the conserved viral gene E1. We confirm immunogenicity of the identified viral peptides in HPV-positive women, and women with cervical intraepithelial neoplasia. We observe consistent transcription of the E1, E6, and E7 genes in 10 primary cervical tumor resections from the four most common high-risk HPV subtypes (HPV16, 18, 31, and 45), suggesting the suitability of E1 as therapeutic target. We finally confirm HLA presentation of canonical peptides derived from E6 and E7, and ARF-derived viral peptides from a reverse-strand transcript spanning the HPV E1 and E2 genes in primary human cervical tumor tissue. Our results extend currently known viral immunotherapeutic targets in cervical cancer and highlight E1 as an important cervical cancer antigen.",

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AU - Peng, Xu

AU - Woodhouse, Isaac

AU - Hancock, Gemma

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AU - Marx, Kristina

AU - Müller, Julius

AU - Salatino, Silvia

AU - Partridge, Thomas

AU - Nicastri, Annalisa

AU - Liao, Hanqing

AU - Kruppa, Gary

AU - Hellner, Karin

AU - Dorrell, Lucy

AU - Ternette, Nicola

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AB - Current immunotherapeutic approaches for human papillomavirus (HPV)-driven cervical cancer target the viral oncogenes E6 and E7. We report viral canonical and alternative reading frame (ARF)-derived sequences presented on cervical tumor cells, including antigens encoded by the conserved viral gene E1. We confirm immunogenicity of the identified viral peptides in HPV-positive women, and women with cervical intraepithelial neoplasia. We observe consistent transcription of the E1, E6, and E7 genes in 10 primary cervical tumor resections from the four most common high-risk HPV subtypes (HPV16, 18, 31, and 45), suggesting the suitability of E1 as therapeutic target. We finally confirm HLA presentation of canonical peptides derived from E6 and E7, and ARF-derived viral peptides from a reverse-strand transcript spanning the HPV E1 and E2 genes in primary human cervical tumor tissue. Our results extend currently known viral immunotherapeutic targets in cervical cancer and highlight E1 as an important cervical cancer antigen.

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KW - Cell biology

KW - Immunology

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Novel canonical and non-canonical viral antigens extend current targets for immunotherapy of HPV-driven cervical cancer

Abstract

Bibliographical note

Funding

Keywords

UN SDGs

Access to Document

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