Loss of HPV type 16 E7 restores cGAS-STING responses in human papilloma virus-positive oropharyngeal squamous cell carcinomas cells

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Bortnik, V
Wu, M
Julcher, B
Salinas, A
Nikolic, I
Simpson, KJ
McMillan, NA
Idris, A
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2020
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Abstract

Human papilloma viruses (HPV) are the main culprit in cervical and oropharyngeal cancers. HPV positive (+) cancers are regarded as ‘oncogene addicted’, displaying an absolute requirement for the continued expression of the oncogenes for their viability owing their survival, and thus making these genes salient targets for developing specific therapeutic agents. There is a strong association between HPV and oropharyngeal squamous cell carcinomas (OPSCC), a subset of head and neck cancers (HNCs). Alarmingly, HPV-associated OPSCC are on the rise globally, and the number of cases of HPV + OPSCCs surpasses that of cervical cancer in the USA. Here, we show that major HPV oncogenes, E6 and E7, are essential for the survival of HPV positive (+) OPSCCs, making these oncogenes salient targets for HPV-driven OPSCCs. HPV E7 is known to interact with STING, a component of the viral DNA-sensing cGAS-STING machinery which activates a pro-typical anti-viral type I interferon (IFN) response. Our recent work showed that E7 from HPV type 16 is responsible for the blockade of cGAS-STING responses in HPV + OPSCC cells. In this study, we show that CRISPR/Cas9-mediated loss of E7 from HPV + OPSCC cells, SCC2 and SCC104, restored cGAS-STING responses. Future work could involve HPV oncogene targeting leading to HPV + OPSCC tumour regression and that the combined use of STING agonists would induce favourable tumour clearance by activating appropriate anti-tumour responses.

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Journal of Microbiology, Immunology and Infection

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© 2020, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, providing that the work is properly cited.

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Immunology

Medical microbiology

Oncology and carcinogenesis

E7

HPV

OPSCC

Oral cancer

STING

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Bortnik, V; Wu, M; Julcher, B; Salinas, A; Nikolic, I; Simpson, KJ; McMillan, NA; Idris, A, Loss of HPV type 16 E7 restores cGAS-STING responses in human papilloma virus-positive oropharyngeal squamous cell carcinomas cells, Journal of Microbiology, Immunology and Infection, 2020

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