Pathogens (Jan 2023)

Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice

  • 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,
  • Angelika B. Riemer

DOI
https://doi.org/10.3390/pathogens12020188
Journal volume & issue
Vol. 12, no. 2
p. 188

Abstract

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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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