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. 2021 Nov 16;13(22):5725.
doi: 10.3390/cancers13225725.

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

Eleni Gkika  1   2   3 , Sonja Adebahr  1   2   3 , Anton Brenner  1 , Tanja Schimek-Jasch  1   2   3 , Gianluca Radicioni  1   2   3 , Jan-Philipp Exner  1   2   3 , Alexander Rühle  1   2   3 , Simon K B Spohn  1   2   3 , Ilinca Popp  1   2   3 , Constantinos Zamboglou  1   2   3 , Tanja Sprave  1   2   3 , Elke Firat  1   2   3 , Gabriele Niedermann  1   2   3 , Nils Henrik Nicolay  1   2   3 , Ursula Nestle  1   4 , Anca-Ligia Grosu  1   2   3 , Dan G Duda  5
Affiliations

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

Eleni Gkika et al. Cancers (Basel). .

Abstract

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: p = 0.039, HR: 1.041, 95% CI: 1.002-1.082, FU1: p = 0.001, HR: 1.139, 95% CI: 1.056-1.228, FU2: p = 0.017, HR: 1.101 95% CI: 1.018-1.192), while IL-8 level correlated with OS at RTduring and RTend (RTduring: p = 0.017, HR: 1.014, 95% CI: 1.002-1.026, RTend: p = 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.

Keywords: esophageal cancer; immune modulation; lung cancer; radiotherapy.

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Conflict of interest statement

D.G.D. received consultant fees from Bayer, BMS, Simcere, Sophia Biosciences, Innocoll and Surface Oncology and research grants from Bayer, Merrimack, Exelixis, BMS and Surface Oncology. No reagents or funding from these companies was used in this study.

Figures

Figure 1
Figure 1
Longitudinal assessment of blood biomarkers in all patients. Detection limits are reported in Table S1. Concentrations are in pg/mL. Statistical differences over time (p < 0.05) compared to baseline are marked with asterisks (*). p values from Wilcoxon test.
Figure 2
Figure 2
Longitudinal assessment of blood biomarkers (A) in lung cancer patients and (B) in esophageal cancer patients. Detection limits are reported in Table S1. Concentrations are in pg/mL. Statistically significant changes (p < 0.05) compared to baseline are marked with an asterisk (*). p values from Wilcoxon test.
Figure 2
Figure 2
Longitudinal assessment of blood biomarkers (A) in lung cancer patients and (B) in esophageal cancer patients. Detection limits are reported in Table S1. Concentrations are in pg/mL. Statistically significant changes (p < 0.05) compared to baseline are marked with an asterisk (*). p values from Wilcoxon test.
Figure 3
Figure 3
Difference between blood biomarkers with different treatment types: (A) radiotherapy (normofractionated vs. stereotactic body radiotherapy vs. hypofractionated radiotherapy); (B) chemotherapy. * p < 0.05; p values from Wilcoxon test compared to baseline.
Figure 3
Figure 3
Difference between blood biomarkers with different treatment types: (A) radiotherapy (normofractionated vs. stereotactic body radiotherapy vs. hypofractionated radiotherapy); (B) chemotherapy. * p < 0.05; p values from Wilcoxon test compared to baseline.
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