Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response
Chemoradiotherapy (CRT) is a standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Unfortunately, not all patients respond to this therapy and require further treatment, either salvage surgery or palliative therapy. The addition of immunotherapy to CRT is currently being inv...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.862694/full |
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| author | Johannes Doescher Johannes Doescher Adrian von Witzleben Konstantinos Boukas Stephanie E. Weissinger Gareth J. Thomas Simon Laban Jaya Thomas Thomas K. Hoffmann Christian H. Ottensmeier |
| author_facet | Johannes Doescher Johannes Doescher Adrian von Witzleben Konstantinos Boukas Stephanie E. Weissinger Gareth J. Thomas Simon Laban Jaya Thomas Thomas K. Hoffmann Christian H. Ottensmeier |
| author_sort | Johannes Doescher |
| collection | DOAJ |
| description | Chemoradiotherapy (CRT) is a standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Unfortunately, not all patients respond to this therapy and require further treatment, either salvage surgery or palliative therapy. The addition of immunotherapy to CRT is currently being investigated and early results describe a mixed response. Therefore, it is important to understand the impact of CRT on the tumor microenvironment (TME) to be able to interpret the results of the clinical trials. Paired biopsies from 30 HNSCC patients were collected before and three months after completion of primary CRT and interrogated for the expression of 1392 immune- and cancer-related genes. There was a relevant difference in the number of differentially expressed genes between the total cohort and patients with residual disease. Genes involved in T cell activation showed significantly reduced expression in these tumors after therapy. Furthermore, gene enrichment for several T cell subsets confirmed this observation. The analysis of tissue resident memory T cells (TRM) did not show a clear association with impaired response to therapy. CRT seems to lead to a loss of T cells in patients with incomplete response that needs to be reversed. It is not clear whether the addition of anti-PD-1 antibodies alone to CRT can prevent treatment failure, as no upregulation of the targets was measurable in the TME. |
| first_indexed | 2024-04-12T22:43:21Z |
| format | Article |
| id | doaj.art-0f6a2dfd86bf46f089d4d00e59c62b60 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-12T22:43:21Z |
| publishDate | 2022-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-0f6a2dfd86bf46f089d4d00e59c62b602022-12-22T03:13:38ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-04-011210.3389/fonc.2022.862694862694Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on ResponseJohannes Doescher0Johannes Doescher1Adrian von Witzleben2Konstantinos Boukas3Stephanie E. Weissinger4Gareth J. Thomas5Simon Laban6Jaya Thomas7Thomas K. Hoffmann8Christian H. Ottensmeier9Translational Immunology Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United KingdomDepartment of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, GermanyDepartment of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, GermanyWessex Investigational Sciences Hub, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, United KingdomInstitute of Pathology, Ulm University Medical Center, Ulm, GermanyWessex Investigational Sciences Hub, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, United KingdomDepartment of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, GermanyWessex Investigational Sciences Hub, University of Southampton, Faculty of Medicine, Southampton General Hospital, Southampton, United KingdomDepartment of Otorhinolaryngology, Head and Neck Surgery, Ulm University Medical Center, Ulm, GermanyTranslational Immunology Group, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, United KingdomChemoradiotherapy (CRT) is a standard treatment for advanced head and neck squamous cell carcinoma (HNSCC). Unfortunately, not all patients respond to this therapy and require further treatment, either salvage surgery or palliative therapy. The addition of immunotherapy to CRT is currently being investigated and early results describe a mixed response. Therefore, it is important to understand the impact of CRT on the tumor microenvironment (TME) to be able to interpret the results of the clinical trials. Paired biopsies from 30 HNSCC patients were collected before and three months after completion of primary CRT and interrogated for the expression of 1392 immune- and cancer-related genes. There was a relevant difference in the number of differentially expressed genes between the total cohort and patients with residual disease. Genes involved in T cell activation showed significantly reduced expression in these tumors after therapy. Furthermore, gene enrichment for several T cell subsets confirmed this observation. The analysis of tissue resident memory T cells (TRM) did not show a clear association with impaired response to therapy. CRT seems to lead to a loss of T cells in patients with incomplete response that needs to be reversed. It is not clear whether the addition of anti-PD-1 antibodies alone to CRT can prevent treatment failure, as no upregulation of the targets was measurable in the TME.https://www.frontiersin.org/articles/10.3389/fonc.2022.862694/fullhead and neck squamous cell carcinomachemoradiotherapytumor microenvironmenttissue resident memory T cellsgene set enrichment |
| spellingShingle | Johannes Doescher Johannes Doescher Adrian von Witzleben Konstantinos Boukas Stephanie E. Weissinger Gareth J. Thomas Simon Laban Jaya Thomas Thomas K. Hoffmann Christian H. Ottensmeier Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response Frontiers in Oncology head and neck squamous cell carcinoma chemoradiotherapy tumor microenvironment tissue resident memory T cells gene set enrichment |
| title | Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response |
| title_full | Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response |
| title_fullStr | Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response |
| title_full_unstemmed | Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response |
| title_short | Changes in Gene Expression Patterns in the Tumor Microenvironment of Head and Neck Squamous Cell Carcinoma Under Chemoradiotherapy Depend on Response |
| title_sort | changes in gene expression patterns in the tumor microenvironment of head and neck squamous cell carcinoma under chemoradiotherapy depend on response |
| topic | head and neck squamous cell carcinoma chemoradiotherapy tumor microenvironment tissue resident memory T cells gene set enrichment |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.862694/full |
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