TY  - JOUR
AU  - Schifflers, Christoph
AU  - Zottnick, Samantha
AU  - Förster, Jonas
AU  - Kruse, Sebastian
AU  - Yang, Ruwen
AU  - Wiethoff, Hendrik
AU  - Bozza, Matthias
AU  - Hoppe-Seyler, Karin
AU  - Heikenwälder, Mathias
AU  - Harbottle, Richard P
AU  - Michiels, Carine
AU  - Riemer, Angelika
TI  - Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice.
JO  - Pathogens
VL  - 12
IS  - 2
SN  - 2076-0817
CY  - Basel
PB  - MDPI
M1  - DKFZ-2023-00490
SP  - 188
PY  - 2023
N1  - #EA:F130#LA:F130#
AB  - 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.
KW  - head and neck squamous cell carcinoma (Other)
KW  - human papillomavirus (Other)
KW  - orthotopic tumor model (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:36839460
C2  - pmc:PMC9958775
DO  - DOI:10.3390/pathogens12020188
UR  - https://inrepo02.dkfz.de/record/274204
ER  -