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

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,...

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Main Authors: Schifflers, Christoph (Author) , Zottnick, Samantha (Author) , Förster, Jonas (Author) , Kruse, Sebastian (Author) , Yang, Ruwen (Author) , Wiethoff, Hendrik (Author) , Bozza, Matthias (Author) , Hoppe-Seyler, Karin (Author) , Heikenwälder, Mathias (Author) , Harbottle, Richard P. (Author) , Michiels, Carine (Author) , Riemer, Angelika (Author)
Format: Article (Journal)
Language:English
Published: 25 January 2023
In: Pathogens
Year: 2023, Volume: 12, Issue: 2, Pages: 1-13
ISSN:2076-0817
DOI:10.3390/pathogens12020188
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/pathogens12020188
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2076-0817/12/2/188
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 30.03.2023
Physical Description:Online Resource
ISSN:2076-0817
DOI:10.3390/pathogens12020188

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