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: | , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
25 January 2023
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| 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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| 520 | |a 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. | ||
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