Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies

The effects of radiotherapy on systemic immunity remain to be fully characterized in a disease-specific manner. The aim of the study was to examine potential biomarkers of systemic immunomodulation when using radiotherapy for thoracic malignancies. Serial blood samples were collected from 56 patient...

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Main Authors: Eleni Gkika, Sonja Adebahr, Anton Brenner, Tanja Schimek-Jasch, Gianluca Radicioni, Jan-Philipp Exner, Alexander Rühle, Simon K. B. Spohn, Ilinca Popp, Constantinos Zamboglou, Tanja Sprave, Elke Firat, Gabriele Niedermann, Nils Henrik Nicolay, Ursula Nestle, Anca-Ligia Grosu, Dan G. Duda
Format: Article
Language:English
Published: MDPI AG 2021-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/13/22/5725
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author Eleni Gkika
Sonja Adebahr
Anton Brenner
Tanja Schimek-Jasch
Gianluca Radicioni
Jan-Philipp Exner
Alexander Rühle
Simon K. B. Spohn
Ilinca Popp
Constantinos Zamboglou
Tanja Sprave
Elke Firat
Gabriele Niedermann
Nils Henrik Nicolay
Ursula Nestle
Anca-Ligia Grosu
Dan G. Duda
author_facet Eleni Gkika
Sonja Adebahr
Anton Brenner
Tanja Schimek-Jasch
Gianluca Radicioni
Jan-Philipp Exner
Alexander Rühle
Simon K. B. Spohn
Ilinca Popp
Constantinos Zamboglou
Tanja Sprave
Elke Firat
Gabriele Niedermann
Nils Henrik Nicolay
Ursula Nestle
Anca-Ligia Grosu
Dan G. Duda
author_sort Eleni Gkika
collection DOAJ
description The effects of radiotherapy on systemic immunity remain to be fully characterized in a disease-specific manner. The aim of the study was to examine potential biomarkers of systemic immunomodulation when using radiotherapy for thoracic malignancies. Serial blood samples were collected from 56 patients with thoracic malignancies prior (RTbaseline), during (RTduring) and at the end of radiotherapy (RTend), as well as at the first (FU1) and second follow-up (FU2). The changes in serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF-α, bFGF, sFlt-1, PlGF, VEGF, VEGF-C, VEGF-D and HGF were measured by multiplexed array and tested for associations with clinical outcomes. We observed an increase in the levels of IL-10, IFN-γ, PlGF and VEGF-D and a decrease in those of IL-8, VEGF, VEGF-C and sFlt-1 during and at the end of radiotherapy. Furthermore, baseline concentration of TNF-α significantly correlated with OS. IL-6 level at RTend and FU1,2 correlated with OS (RTend: <i>p</i> = 0.039, HR: 1.041, 95% CI: 1.002–1.082, FU1: <i>p</i> = 0.001, HR: 1.139, 95% CI: 1.056–1.228, FU2: <i>p</i> = 0.017, HR: 1.101 95% CI: 1.018–1.192), while IL-8 level correlated with OS at RTduring and RTend (RTduring: <i>p</i> = 0.017, HR: 1.014, 95% CI: 1.002–1.026, RTend: <i>p</i> = 0.004, HR: 1.007, 95% CI: 1.061–1.686). In conclusion, serum levels of TNF-α, IL-6 and IL-8 are potential biomarkers of response to radiotherapy. Given the recent implementation of immunotherapy in lung and esophageal cancer, these putative blood biomarkers should be further validated and evaluated in the combination or sequential therapy setting.
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spelling doaj.art-6247631eac80406790b793b1a65fd9b02023-11-22T22:42:23ZengMDPI AGCancers2072-66942021-11-011322572510.3390/cancers13225725Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic MalignanciesEleni Gkika0Sonja Adebahr1Anton Brenner2Tanja Schimek-Jasch3Gianluca Radicioni4Jan-Philipp Exner5Alexander Rühle6Simon K. B. Spohn7Ilinca Popp8Constantinos Zamboglou9Tanja Sprave10Elke Firat11Gabriele Niedermann12Nils Henrik Nicolay13Ursula Nestle14Anca-Ligia Grosu15Dan G. Duda16University Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyUniversity Medical Center Freiburg, Department of Radiation Oncology, Faculty of Medicine, University of Freiburg, 79106 Freiburg, GermanyE. L. Steele Laboratories for Tumor Biology, Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USAThe effects of radiotherapy on systemic immunity remain to be fully characterized in a disease-specific manner. The aim of the study was to examine potential biomarkers of systemic immunomodulation when using radiotherapy for thoracic malignancies. Serial blood samples were collected from 56 patients with thoracic malignancies prior (RTbaseline), during (RTduring) and at the end of radiotherapy (RTend), as well as at the first (FU1) and second follow-up (FU2). The changes in serum levels of IL-10, IFN-γ, IL-12p70, IL-13, IL-1β, IL-4, IL-6, IL-8, TNF-α, bFGF, sFlt-1, PlGF, VEGF, VEGF-C, VEGF-D and HGF were measured by multiplexed array and tested for associations with clinical outcomes. We observed an increase in the levels of IL-10, IFN-γ, PlGF and VEGF-D and a decrease in those of IL-8, VEGF, VEGF-C and sFlt-1 during and at the end of radiotherapy. Furthermore, baseline concentration of TNF-α significantly correlated with OS. IL-6 level at RTend and FU1,2 correlated with OS (RTend: <i>p</i> = 0.039, HR: 1.041, 95% CI: 1.002–1.082, FU1: <i>p</i> = 0.001, HR: 1.139, 95% CI: 1.056–1.228, FU2: <i>p</i> = 0.017, HR: 1.101 95% CI: 1.018–1.192), while IL-8 level correlated with OS at RTduring and RTend (RTduring: <i>p</i> = 0.017, HR: 1.014, 95% CI: 1.002–1.026, RTend: <i>p</i> = 0.004, HR: 1.007, 95% CI: 1.061–1.686). In conclusion, serum levels of TNF-α, IL-6 and IL-8 are potential biomarkers of response to radiotherapy. Given the recent implementation of immunotherapy in lung and esophageal cancer, these putative blood biomarkers should be further validated and evaluated in the combination or sequential therapy setting.https://www.mdpi.com/2072-6694/13/22/5725radiotherapyimmune modulationlung canceresophageal cancer
spellingShingle Eleni Gkika
Sonja Adebahr
Anton Brenner
Tanja Schimek-Jasch
Gianluca Radicioni
Jan-Philipp Exner
Alexander Rühle
Simon K. B. Spohn
Ilinca Popp
Constantinos Zamboglou
Tanja Sprave
Elke Firat
Gabriele Niedermann
Nils Henrik Nicolay
Ursula Nestle
Anca-Ligia Grosu
Dan G. Duda
Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
Cancers
radiotherapy
immune modulation
lung cancer
esophageal cancer
title Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
title_full Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
title_fullStr Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
title_full_unstemmed Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
title_short Changes in Blood Biomarkers of Angiogenesis and Immune Modulation after Radiation Therapy and Their Association with Outcomes in Thoracic Malignancies
title_sort changes in blood biomarkers of angiogenesis and immune modulation after radiation therapy and their association with outcomes in thoracic malignancies
topic radiotherapy
immune modulation
lung cancer
esophageal cancer
url https://www.mdpi.com/2072-6694/13/22/5725
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