Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice
For the development and evaluation of new head and neck squamous cell carcinoma (HNSCC) therapeutics, suitable, well-characterized animal models are needed. Thus, by analyzing orthotopic versus subcutaneous models of HNSCC in immunocompetent mice, we evaluated the existence of adenosine-related immu...
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| Format: | Article |
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/1/247 |
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| author | Matthias Brand Simon Laban Marie-Nicole Theodoraki Johannes Doescher Thomas K. Hoffmann Patrick J. Schuler Cornelia Brunner |
| author_facet | Matthias Brand Simon Laban Marie-Nicole Theodoraki Johannes Doescher Thomas K. Hoffmann Patrick J. Schuler Cornelia Brunner |
| author_sort | Matthias Brand |
| collection | DOAJ |
| description | For the development and evaluation of new head and neck squamous cell carcinoma (HNSCC) therapeutics, suitable, well-characterized animal models are needed. Thus, by analyzing orthotopic versus subcutaneous models of HNSCC in immunocompetent mice, we evaluated the existence of adenosine-related immunosuppressive B- and T lymphocyte populations within the tumor microenvironment (TME). Applying the SCC VII model for the induction of HNSCC in immunocompetent C3H/HeN mice, the cellular TME was characterized after tumor initiation over time by flow cytometry. The TME in orthotopic grown tumors revealed a larger population of tumor-infiltrating lymphocytes (TIL) with more B cells and CD4<sup>+</sup> T cells than the subcutaneously grown tumors. Immune cell populations in the blood and bone marrow showed a rather distinct reaction toward tumor induction and tumor location compared to the spleen, lymph nodes, or thymus. In addition, large numbers of immunosuppressive B- and T cells were identified within the TME but also in secondary lymphoid organs, independently of the tumor initiation site. The altered immunogenic TME may influence the response to any treatment attempt. Moreover, when analyzing the TME and other lymphoid organs of tumor-bearing mice, we observed conditions reflecting largely those of patients suffering from HNSCC suggesting the C3H/HeN mouse model as a suitable tool for studies aiming to target immunosuppression to improve anti-cancer therapies. |
| first_indexed | 2024-03-10T13:42:17Z |
| format | Article |
| id | doaj.art-1545f9a27a4a494eaa00884f5b8c392e |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T13:42:17Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1545f9a27a4a494eaa00884f5b8c392e2023-11-21T02:54:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122124710.3390/ijms22010247Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent MiceMatthias Brand0Simon Laban1Marie-Nicole Theodoraki2Johannes Doescher3Thomas K. Hoffmann4Patrick J. Schuler5Cornelia Brunner6Department of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyDepartment of Otorhinolaryngology, University Hospital Ulm, Frauensteige 12, 89075 Ulm, GermanyFor the development and evaluation of new head and neck squamous cell carcinoma (HNSCC) therapeutics, suitable, well-characterized animal models are needed. Thus, by analyzing orthotopic versus subcutaneous models of HNSCC in immunocompetent mice, we evaluated the existence of adenosine-related immunosuppressive B- and T lymphocyte populations within the tumor microenvironment (TME). Applying the SCC VII model for the induction of HNSCC in immunocompetent C3H/HeN mice, the cellular TME was characterized after tumor initiation over time by flow cytometry. The TME in orthotopic grown tumors revealed a larger population of tumor-infiltrating lymphocytes (TIL) with more B cells and CD4<sup>+</sup> T cells than the subcutaneously grown tumors. Immune cell populations in the blood and bone marrow showed a rather distinct reaction toward tumor induction and tumor location compared to the spleen, lymph nodes, or thymus. In addition, large numbers of immunosuppressive B- and T cells were identified within the TME but also in secondary lymphoid organs, independently of the tumor initiation site. The altered immunogenic TME may influence the response to any treatment attempt. Moreover, when analyzing the TME and other lymphoid organs of tumor-bearing mice, we observed conditions reflecting largely those of patients suffering from HNSCC suggesting the C3H/HeN mouse model as a suitable tool for studies aiming to target immunosuppression to improve anti-cancer therapies.https://www.mdpi.com/1422-0067/22/1/247tumor microenvironmenthead and neck cancerSCC VII orthotopic mouse modelSCC VII subcutaneous mouse modelregulatory B cellsCD4<sup>+</sup> T cells |
| spellingShingle | Matthias Brand Simon Laban Marie-Nicole Theodoraki Johannes Doescher Thomas K. Hoffmann Patrick J. Schuler Cornelia Brunner Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice International Journal of Molecular Sciences tumor microenvironment head and neck cancer SCC VII orthotopic mouse model SCC VII subcutaneous mouse model regulatory B cells CD4<sup>+</sup> T cells |
| title | Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice |
| title_full | Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice |
| title_fullStr | Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice |
| title_full_unstemmed | Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice |
| title_short | Characterization and Differentiation of the Tumor Microenvironment (TME) of Orthotopic and Subcutaneously Grown Head and Neck Squamous Cell Carcinoma (HNSCC) in Immunocompetent Mice |
| title_sort | characterization and differentiation of the tumor microenvironment tme of orthotopic and subcutaneously grown head and neck squamous cell carcinoma hnscc in immunocompetent mice |
| topic | tumor microenvironment head and neck cancer SCC VII orthotopic mouse model SCC VII subcutaneous mouse model regulatory B cells CD4<sup>+</sup> T cells |
| url | https://www.mdpi.com/1422-0067/22/1/247 |
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