%0 Journal Article
%A Schifflers, Christoph
%A Zottnick, Samantha
%A Förster, Jonas
%A Kruse, Sebastian
%A Yang, Ruwen
%A Wiethoff, Hendrik
%A Bozza, Matthias
%A Hoppe-Seyler, Karin
%A Heikenwälder, Mathias
%A Harbottle, Richard P
%A Michiels, Carine
%A Riemer, Angelika
%T Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice.
%J Pathogens
%V 12
%N 2
%@ 2076-0817
%C Basel
%I MDPI
%M DKFZ-2023-00490
%P 188
%D 2023
%Z #EA:F130#LA:F130#
%X 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.
%K head and neck squamous cell carcinoma (Other)
%K human papillomavirus (Other)
%K orthotopic tumor model (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36839460
%2 pmc:PMC9958775
%R 10.3390/pathogens12020188
%U https://inrepo02.dkfz.de/record/274204