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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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Hauptverfasser: Schifflers, Christoph (VerfasserIn) , Zottnick, Samantha (VerfasserIn) , Förster, Jonas (VerfasserIn) , Kruse, Sebastian (VerfasserIn) , Yang, Ruwen (VerfasserIn) , Wiethoff, Hendrik (VerfasserIn) , Bozza, Matthias (VerfasserIn) , Hoppe-Seyler, Karin (VerfasserIn) , Heikenwälder, Mathias (VerfasserIn) , Harbottle, Richard P. (VerfasserIn) , Michiels, Carine (VerfasserIn) , Riemer, Angelika (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 25 January 2023
In: Pathogens
Year: 2023, Jahrgang: 12, Heft: 2, Pages: 1-13
ISSN:2076-0817
DOI:10.3390/pathogens12020188
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/pathogens12020188
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2076-0817/12/2/188
Volltext
Verfasserangaben: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
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 30.03.2023
Beschreibung:Online Resource
ISSN:2076-0817
DOI:10.3390/pathogens12020188

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