Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy
BackgroundEsophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the imp...
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Frontiers Media S.A.
2024-12-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509051/full |
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| author | Lovis Hampe Stefan Küffer Tim Niemeier Niklas Christian Scheele Laetitia Zoe Hampe Anna Luisa Riedl Laura Anna Fischer David Alexander Ziegler Martin Leu Leif Hendrik Dröge Alexander König Michael Ghadimi Friederike Braulke Stefan Rieken Hanibal Bohnenberger Rami A. El Shafie |
| author_facet | Lovis Hampe Stefan Küffer Tim Niemeier Niklas Christian Scheele Laetitia Zoe Hampe Anna Luisa Riedl Laura Anna Fischer David Alexander Ziegler Martin Leu Leif Hendrik Dröge Alexander König Michael Ghadimi Friederike Braulke Stefan Rieken Hanibal Bohnenberger Rami A. El Shafie |
| author_sort | Lovis Hampe |
| collection | DOAJ |
| description | BackgroundEsophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the impact of neoadjuvant CRT on PD-L1 surface expression in esophageal cancer both in vitro and in vivo considering its implications for immunotherapy.MethodsPD-L1 expression dynamics were assessed in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) cell lines (OE-33, FLO-1, KYSE-180) treated with Carboplatin, Paclitaxel, radiotherapy (RT), and CRT. PD-L1 expression was measured by flow cytometry at 48- and 72 hours post-treatment. Temporal changes of surface PD-L1 were further investigated in KYSE-180 cells following RT, up to 168h after treatment. Additionally, PD-L1 expression was analyzed via immunohistochemistry in histological samples from 19 patients (9 EAC, 10 ESCC) treated with neoadjuvant CRT according to the CROSS-scheme.ResultsPD-L1 expression was upregulated the most by Carboplatin, a combination of chemotherapy, or CRT in all cell lines. Higher irradiation doses were more effective in inducing PD-L1 expression, while Paclitaxel alone did not consistently increase PD-L1. The ESCC cell line KYSE-180 showed the highest relative PD-L1 increase. Measurement of PD-L1 kinetics revealed a transient upregulation of surface PD-L1, which peaked at 72 hours post-treatment and subsequently returned to baseline levels by 168 hours. In vivo, data demonstrated no significant PD-L1 expression changes when comparing pre- and post-treatment levels.ConclusionsChemotherapy, RT, and CRT can induce PD-L1 expression in various esophageal cancer cell lines. However, neoadjuvant CRT according to the CROSS protocol does not significantly induce PD-L1 in vivo. Considering the difference in time between pre- and post-therapeutic measurements, these findings suggest that PD-L1 upregulation due to neoadjuvant therapy may be transient in vivo as well. This highlights the potential benefit of administering immunotherapy in a neoadjuvant setting. |
| format | Article |
| id | doaj-art-17151c4d45e3441bbf28a888f6e6f5ab |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Frontiers Media S.A. |
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| spelling | doaj-art-17151c4d45e3441bbf28a888f6e6f5ab2025-08-20T02:32:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-12-011510.3389/fimmu.2024.15090511509051Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapyLovis Hampe0Stefan Küffer1Tim Niemeier2Niklas Christian Scheele3Laetitia Zoe Hampe4Anna Luisa Riedl5Laura Anna Fischer6David Alexander Ziegler7Martin Leu8Leif Hendrik Dröge9Alexander König10Michael Ghadimi11Friederike Braulke12Stefan Rieken13Hanibal Bohnenberger14Rami A. El Shafie15Translational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Pathology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyDepartment of General, Visceral and Thoracic Surgery, University Hospital, Hamburg, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyDepartment of Gastroenterology and Gastrointestinal Oncology, University Medical Center, Göttingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center, Göttingen, GermanyGöttingen Comprehensive Cancer Center (G-CCC), University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyInstitute of Pathology, University Medical Center Göttingen, Göttingen, GermanyTranslational Radiobiology Lab, Department of Radiotherapy and Radiation Oncology, University Medical Center Göttingen, Göttingen, GermanyBackgroundEsophageal cancer has a poor prognosis despite treatment advancements. Although the benefit of neoadjuvant chemoradiotherapy (CRT) followed by adjuvant immunotherapy is evident, the effects of CRT on PD-L1 expression in esophageal cancer are not well understood. This study examines the impact of neoadjuvant CRT on PD-L1 surface expression in esophageal cancer both in vitro and in vivo considering its implications for immunotherapy.MethodsPD-L1 expression dynamics were assessed in esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) cell lines (OE-33, FLO-1, KYSE-180) treated with Carboplatin, Paclitaxel, radiotherapy (RT), and CRT. PD-L1 expression was measured by flow cytometry at 48- and 72 hours post-treatment. Temporal changes of surface PD-L1 were further investigated in KYSE-180 cells following RT, up to 168h after treatment. Additionally, PD-L1 expression was analyzed via immunohistochemistry in histological samples from 19 patients (9 EAC, 10 ESCC) treated with neoadjuvant CRT according to the CROSS-scheme.ResultsPD-L1 expression was upregulated the most by Carboplatin, a combination of chemotherapy, or CRT in all cell lines. Higher irradiation doses were more effective in inducing PD-L1 expression, while Paclitaxel alone did not consistently increase PD-L1. The ESCC cell line KYSE-180 showed the highest relative PD-L1 increase. Measurement of PD-L1 kinetics revealed a transient upregulation of surface PD-L1, which peaked at 72 hours post-treatment and subsequently returned to baseline levels by 168 hours. In vivo, data demonstrated no significant PD-L1 expression changes when comparing pre- and post-treatment levels.ConclusionsChemotherapy, RT, and CRT can induce PD-L1 expression in various esophageal cancer cell lines. However, neoadjuvant CRT according to the CROSS protocol does not significantly induce PD-L1 in vivo. Considering the difference in time between pre- and post-therapeutic measurements, these findings suggest that PD-L1 upregulation due to neoadjuvant therapy may be transient in vivo as well. This highlights the potential benefit of administering immunotherapy in a neoadjuvant setting.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509051/fullesophageal cancerimmunotherapyprogrammed-death-ligand-1checkmate-577CROSS |
| spellingShingle | Lovis Hampe Stefan Küffer Tim Niemeier Niklas Christian Scheele Laetitia Zoe Hampe Anna Luisa Riedl Laura Anna Fischer David Alexander Ziegler Martin Leu Leif Hendrik Dröge Alexander König Michael Ghadimi Friederike Braulke Stefan Rieken Hanibal Bohnenberger Rami A. El Shafie Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy Frontiers in Immunology esophageal cancer immunotherapy programmed-death-ligand-1 checkmate-577 CROSS |
| title | Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy |
| title_full | Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy |
| title_fullStr | Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy |
| title_full_unstemmed | Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy |
| title_short | Effects of chemoradiotherapy on surface PD-L1 expression in esophageal cancer and its implications for immunotherapy |
| title_sort | effects of chemoradiotherapy on surface pd l1 expression in esophageal cancer and its implications for immunotherapy |
| topic | esophageal cancer immunotherapy programmed-death-ligand-1 checkmate-577 CROSS |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1509051/full |
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