Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy
Abstract Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC pat...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | Radiation Oncology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13014-022-02153-9 |
| _version_ | 1798016805485150208 |
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| author | Alexander Rühle Jovan Todorovic Simon S. K. Spohn Eleni Gkika Christoph Becker Andreas Knopf Constantinos Zamboglou Tanja Sprave Martin Werner Anca-Ligia Grosu Gian Kayser Nils H. Nicolay |
| author_facet | Alexander Rühle Jovan Todorovic Simon S. K. Spohn Eleni Gkika Christoph Becker Andreas Knopf Constantinos Zamboglou Tanja Sprave Martin Werner Anca-Ligia Grosu Gian Kayser Nils H. Nicolay |
| author_sort | Alexander Rühle |
| collection | DOAJ |
| description | Abstract Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population. Material and methods Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses. Results While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels. Conclusion LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC. |
| first_indexed | 2024-04-11T15:56:33Z |
| format | Article |
| id | doaj.art-1e1becab28f1449e921cca6d2bc72d54 |
| institution | Directory Open Access Journal |
| issn | 1748-717X |
| language | English |
| last_indexed | 2024-04-11T15:56:33Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Radiation Oncology |
| spelling | doaj.art-1e1becab28f1449e921cca6d2bc72d542022-12-22T04:15:09ZengBMCRadiation Oncology1748-717X2022-11-0117111210.1186/s13014-022-02153-9Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapyAlexander Rühle0Jovan Todorovic1Simon S. K. Spohn2Eleni Gkika3Christoph Becker4Andreas Knopf5Constantinos Zamboglou6Tanja Sprave7Martin Werner8Anca-Ligia Grosu9Gian Kayser10Nils H. Nicolay11Department of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgInstitute of Surgical Pathology, Department of Pathology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Otorhinolaryngology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Otorhinolaryngology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgInstitute of Surgical Pathology, Department of Pathology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgInstitute of Surgical Pathology, Department of Pathology, Medical Center, Faculty of Medicine, University of FreiburgDepartment of Radiation Oncology, Medical Center, Faculty of Medicine, University of FreiburgAbstract Background and purpose Tumor-infiltrating lymphocytes (TILs) are associated with locoregional control (LRC) in head-and-neck squamous cell carcinoma (HNSCC) patients undergoing (chemo)radiotherapy. As immunosenescence results in reduced immune activity, the role of TILs in elderly HNSCC patients may differ compared to younger patients, providing a rationale to study the prognostic role of TILs and immune checkpoints (ICs) in this population. Material and methods Sixty-three HNSCC patients aged ≥ 65 years undergoing definitive (chemo)radiotherapy between 2010 and 2019 with sufficient material from pre-treatment biopsies were included in the analysis. Immunohistochemical stainings of CD3, CD4, CD8, PD-L1, TIM3, LAG3, TIGIT and CD96, and of osteopontin as an immunosenescence-associated protein were performed. Overall survival (OS) and progression-free survival (PFS) were determined using the Kaplan–Meier method, and Fine-Gray's models were used for locoregional failure (LRF) analyses. Results While there was no correlation between patient age and IC expression, osteopontin levels correlated with increasing age (r = 0.322, p < 0.05). Two-year OS, PFS, and LRC were 44%, 34%, and 71%, respectively. Increased LAG3 expression, both intraepithelial (SHR = 0.33, p < 0.05) and stromal (SHR = 0.38, p < 0.05), and elevated stromal TIM3 expression (SHR = 0.32, p < 0.05) corresponded with reduced LRFs. Absent tumoral PD-L1 expression (TPS = 0%) was associated with more LRFs (SHR = 0.28, p < 0.05). There was a trend towards improved LRF rates in elderly patients with increased intraepithelial CD3 + (SHR = 0.52, p = 0.07) and CD8 + (SHR = 0.52, p = 0.09) TIL levels. Conclusion LAG3, TIM3 and TPS are promising biomarkers in elderly HNSCC patients receiving (chemo)radiotherapy. Considering the frequency of non-cancer related deaths in this population, the prognostic value of these biomarkers primarily relates to LRC.https://doi.org/10.1186/s13014-022-02153-9Head-and-neck cancerElderlyGeriatricImmunosenescenceImmune checkpointTumor-infiltrating lymphocytes |
| spellingShingle | Alexander Rühle Jovan Todorovic Simon S. K. Spohn Eleni Gkika Christoph Becker Andreas Knopf Constantinos Zamboglou Tanja Sprave Martin Werner Anca-Ligia Grosu Gian Kayser Nils H. Nicolay Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy Radiation Oncology Head-and-neck cancer Elderly Geriatric Immunosenescence Immune checkpoint Tumor-infiltrating lymphocytes |
| title | Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy |
| title_full | Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy |
| title_fullStr | Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy |
| title_full_unstemmed | Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy |
| title_short | Prognostic value of tumor-infiltrating immune cells and immune checkpoints in elderly head-and-neck squamous cell carcinoma patients undergoing definitive (chemo)radiotherapy |
| title_sort | prognostic value of tumor infiltrating immune cells and immune checkpoints in elderly head and neck squamous cell carcinoma patients undergoing definitive chemo radiotherapy |
| topic | Head-and-neck cancer Elderly Geriatric Immunosenescence Immune checkpoint Tumor-infiltrating lymphocytes |
| url | https://doi.org/10.1186/s13014-022-02153-9 |
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