Development of an orthotopic HPV16-dependent base of tongue tumor model in MHC-humanized mice

• Verfasst von: Schifflers, Christoph [VerfasserIn]
• Verfasst von: Zottnick, Samantha [VerfasserIn]
• Verfasst von: Förster, Jonas [VerfasserIn]
• Verfasst von: Kruse, Sebastian [VerfasserIn]
• Verfasst von: Yang, Ruwen [VerfasserIn]
• Verfasst von: Wiethoff, Hendrik [VerfasserIn]
• Verfasst von: Bozza, Matthias [VerfasserIn]
• Verfasst von: Hoppe-Seyler, Karin [VerfasserIn]
• Verfasst von: Heikenwälder, Mathias [VerfasserIn]
• Verfasst von: Harbottle, Richard P. [VerfasserIn]
• Verfasst von: Michiels, Carine [VerfasserIn]
• Verfasst von: Riemer, Angelika [VerfasserIn]
• Titel: Development of an orthotopic HPV16-dependent base of tongue tumor model in MHC-humanized mice
• Verf.angabe: Christoph Schifflers, Samantha Zottnick, Jonas D. Förster, Sebastian Kruse, Ruwen Yang, Hendrik Wiethoff, Matthias Bozza, Karin Hoppe-Seyler, Mathias Heikenwälder, Richard P. Harbottle, Carine Michiels and Angelika B. Riemer
• E-Jahr: 2023
• Jahr: 25 January 2023
• Umfang: 13 S.
• Fussnoten: Gesehen am 30.03.2023
• Titel Quelle: Enthalten in: Pathogens
• Ort Quelle: Basel : MDPI, 2012
• Jahr Quelle: 2023
• Band/Heft Quelle: 12(2023), 2 vom: Jan., Artikel-ID 188, Seite 1-13
• ISSN Quelle: 2076-0817
• DOI: doi:10.3390/pathogens12020188
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: head and neck squamous cell carcinoma
• Sach-SW: human papillomavirus
• Sach-SW: orthotopic tumor model
• K10plus-PPN: 1840563192

Abstract

Head and neck squamous cell carcinomas (HNSCC) caused by infections with high-risk human papillomaviruses (HPV) are responsible for an increasing number of head and neck cancers, particularly in the oropharynx. Despite the significant biological differences between HPV-driven and HPV-negative HNSCC, treatment strategies are similar and not HPV targeted. HPV-driven HNSCC are known to be more sensitive to treatment, particularly to radiotherapy, which is at least partially due to HPV-induced immunogenicity. The development of novel therapeutic strategies that are specific for HPV-driven cancers requires tumor models that reflect as closely as possible the characteristics and complexity of human tumors and their response to treatment. Current HPV-positive cancer models lack one or more hallmarks of their human counterpart. This study presents the development of a new HPV16 oncoprotein-dependent tumor model in MHC-humanized mice, modeling the major biologic features of HPV-driven tumors and presenting HLA-A2-restricted HPV16 epitopes. Furthermore, this model was developed to be orthotopic (base of tongue). Thus, it also reflects the correct tumor microenvironment of HPV-driven HNSCC. The cancer cells are implanted in a manner that allows the exact control of the anatomical location of the developing tumor, thereby homogenizing tumor growth. In conclusion, the new model is suited to study HPV16-specific therapeutic vaccinations and other immunotherapies, as well as tumor-targeted interventions, such as surgery or radiotherapy, or a combination of all these modalities.