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,...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-01-01
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| Series: | Pathogens |
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| Online Access: | https://www.mdpi.com/2076-0817/12/2/188 |
| _version_ | 1797618872376885248 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Christoph Schifflers |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T08:18:43Z |
| format | Article |
| id | doaj.art-348fbcb7b76447cfac696a7379748075 |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-11T08:18:43Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-348fbcb7b76447cfac696a73797480752023-11-16T22:33:14ZengMDPI AGPathogens2076-08172023-01-0112218810.3390/pathogens12020188Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized MiceChristoph Schifflers0Samantha Zottnick1Jonas D. Förster2Sebastian Kruse3Ruwen Yang4Hendrik Wiethoff5Matthias Bozza6Karin Hoppe-Seyler7Mathias Heikenwälder8Richard P. Harbottle9Carine Michiels10Angelika B. Riemer11Immunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyImmunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyImmunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyImmunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyViral Transformation Mechanisms, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyInstitute of Pathology, Heidelberg University Hospital, 69120 Heidelberg, GermanyDNA Vector Laboratory, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyMolecular Therapy of Virus-Associated Cancers, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyChronic Inflammation and Cancer, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyDNA Vector Laboratory, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyCell Biology Research Unit (URBC)–Namur Research Institute for Life Sciences (NARILIS), University of Namur, 5000 Namur, BelgiumImmunotherapy and Immunoprevention, German Cancer Research Center (DKFZ), 69120 Heidelberg, GermanyHead 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.https://www.mdpi.com/2076-0817/12/2/188head and neck squamous cell carcinomahuman papillomavirusorthotopic tumor model |
| spellingShingle | 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 Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice Pathogens head and neck squamous cell carcinoma human papillomavirus orthotopic tumor model |
| title | Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice |
| title_full | Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice |
| title_fullStr | Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice |
| title_full_unstemmed | Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice |
| title_short | Development of an Orthotopic HPV16-Dependent Base of Tongue Tumor Model in MHC-Humanized Mice |
| title_sort | development of an orthotopic hpv16 dependent base of tongue tumor model in mhc humanized mice |
| topic | head and neck squamous cell carcinoma human papillomavirus orthotopic tumor model |
| url | https://www.mdpi.com/2076-0817/12/2/188 |
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