A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer
BackgroundDeconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments.MethodsTranscriptom...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264093/full |
| _version_ | 1797650160987144192 |
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| author | Jana Mourtada Jana Mourtada Christelle Lony Christelle Lony Anaïs Nicol Justine De Azevedo Justine De Azevedo Cyril Bour Cyril Bour Christine Macabre Christine Macabre Christine Macabre Patrick Roncarati Sonia Ledrappier Philippe Schultz Christian Borel Mickaël Burgy Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Georg Mellitzer Michaël Herfs Christian Gaiddon Alain C. Jung Alain C. Jung Alain C. Jung |
| author_facet | Jana Mourtada Jana Mourtada Christelle Lony Christelle Lony Anaïs Nicol Justine De Azevedo Justine De Azevedo Cyril Bour Cyril Bour Christine Macabre Christine Macabre Christine Macabre Patrick Roncarati Sonia Ledrappier Philippe Schultz Christian Borel Mickaël Burgy Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Georg Mellitzer Michaël Herfs Christian Gaiddon Alain C. Jung Alain C. Jung Alain C. Jung |
| author_sort | Jana Mourtada |
| collection | DOAJ |
| description | BackgroundDeconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments.MethodsTranscriptomic data from HPV-positive OSCC samples were analyzed using unsupervised hierarchical clustering, and clinical relevance was evaluated using Kaplan-Meier analysis. HPV-positive OSCC cell line models were used in functional analyses and phenotypic assays to assess cell migration and invasion, response to cisplatin, and phagocytosis by macrophages in vitro.ResultsWe found, by transcriptomic analysis of HPV-positive OSCC samples, a ΔNp63 dependent molecular signature that is associated with patient prognosis. ΔNp63 was found to act as a tumor suppressor in HPV-positive OSCC at multiple levels. It inhibits cell migration and invasion, and favors response to chemotherapy. RNA-Seq analysis uncovered an unexpected regulation of genes, such as DKK3, which are involved in immune response-signalling pathways. In agreement with these observations, we found that ΔNp63 expression levels correlate with an enhanced anti-tumor immune environment in OSCC, and ΔNp63 promotes cancer cell phagocytosis by macrophages through a DKK3/NF-κB-dependent pathway.ConclusionOur findings are the first comprehensive identification of molecular mechanisms involved in the heterogeneous prognosis of HPV-positive OSCC, paving the way for much-needed biomarkers and targeted treatment. |
| first_indexed | 2024-03-11T15:56:16Z |
| format | Article |
| id | doaj.art-bf2a6ac09adb4bfcbe807400b5a4314a |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-11T15:56:16Z |
| publishDate | 2023-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-bf2a6ac09adb4bfcbe807400b5a4314a2023-10-25T10:23:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-10-011410.3389/fimmu.2023.12640931264093A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancerJana Mourtada0Jana Mourtada1Christelle Lony2Christelle Lony3Anaïs Nicol4Justine De Azevedo5Justine De Azevedo6Cyril Bour7Cyril Bour8Christine Macabre9Christine Macabre10Christine Macabre11Patrick Roncarati12Sonia Ledrappier13Philippe Schultz14Christian Borel15Mickaël Burgy16Bohdan Wasylyk17Bohdan Wasylyk18Bohdan Wasylyk19Bohdan Wasylyk20Georg Mellitzer21Michaël Herfs22Christian Gaiddon23Alain C. Jung24Alain C. Jung25Alain C. Jung26Laboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratoire de Radiobiologie, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceLaboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceTumorothèque du Centre Paul Strauss, Centre Paul Strauss, Strasbourg, FranceLaboratory of Experimental Pathology, GIGA-Cancer, University of Liège, Liège, BelgiumTumorothèque du Centre Paul Strauss, Centre Paul Strauss, Strasbourg, FranceHôpitaux Universitaires de Strasbourg, Department of Otorhinolaryngology and Head and Neck Surgery, Strasbourg, FranceDepartment of Medical Oncology, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceDepartment of Medical Oncology, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceDepartment of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Illkirch-Graffenstaden, FranceInstitut National de la Santé et de la Recherche Médicale (INSERM) U 1258, Illkirch-Graffenstaden, France0Centre Nationale de la Recherche Scientifique (CNRS) UMR 7104, Illkirch-Graffenstaden, France1Université de Strasbourg, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratory of Experimental Pathology, GIGA-Cancer, University of Liège, Liège, BelgiumUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceLaboratoire de Biologie Tumorale, Institut de cancérologie Strasbourg Europe, Strasbourg, FranceUniversité de Strasbourg-Inserm, UMR_S 1113 IRFAC, Laboratory « Streinth », Strasbourg, FranceTumorothèque du Centre Paul Strauss, Centre Paul Strauss, Strasbourg, FranceBackgroundDeconvoluting the heterogenous prognosis of Human Papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OSCC) is crucial for enhancing patient care, given its rapidly increasing incidence in western countries and the adverse side effects of OSCC treatments.MethodsTranscriptomic data from HPV-positive OSCC samples were analyzed using unsupervised hierarchical clustering, and clinical relevance was evaluated using Kaplan-Meier analysis. HPV-positive OSCC cell line models were used in functional analyses and phenotypic assays to assess cell migration and invasion, response to cisplatin, and phagocytosis by macrophages in vitro.ResultsWe found, by transcriptomic analysis of HPV-positive OSCC samples, a ΔNp63 dependent molecular signature that is associated with patient prognosis. ΔNp63 was found to act as a tumor suppressor in HPV-positive OSCC at multiple levels. It inhibits cell migration and invasion, and favors response to chemotherapy. RNA-Seq analysis uncovered an unexpected regulation of genes, such as DKK3, which are involved in immune response-signalling pathways. In agreement with these observations, we found that ΔNp63 expression levels correlate with an enhanced anti-tumor immune environment in OSCC, and ΔNp63 promotes cancer cell phagocytosis by macrophages through a DKK3/NF-κB-dependent pathway.ConclusionOur findings are the first comprehensive identification of molecular mechanisms involved in the heterogeneous prognosis of HPV-positive OSCC, paving the way for much-needed biomarkers and targeted treatment.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264093/fullΔNp63immune responsehuman papillomavirusoropharyngeal squamous cell carcinomatumor microenvironment |
| spellingShingle | Jana Mourtada Jana Mourtada Christelle Lony Christelle Lony Anaïs Nicol Justine De Azevedo Justine De Azevedo Cyril Bour Cyril Bour Christine Macabre Christine Macabre Christine Macabre Patrick Roncarati Sonia Ledrappier Philippe Schultz Christian Borel Mickaël Burgy Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Bohdan Wasylyk Georg Mellitzer Michaël Herfs Christian Gaiddon Alain C. Jung Alain C. Jung Alain C. Jung A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer Frontiers in Immunology ΔNp63 immune response human papillomavirus oropharyngeal squamous cell carcinoma tumor microenvironment |
| title | A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer |
| title_full | A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer |
| title_fullStr | A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer |
| title_full_unstemmed | A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer |
| title_short | A novel ΔNp63-dependent immune mechanism improves prognosis of HPV-related head and neck cancer |
| title_sort | novel δnp63 dependent immune mechanism improves prognosis of hpv related head and neck cancer |
| topic | ΔNp63 immune response human papillomavirus oropharyngeal squamous cell carcinoma tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1264093/full |
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