Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulat
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ORIGINAL ARTICLE
Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy B. Frey1 · J. Mika2 · K. Jelonek3 · L. Cruz-Garcia4 · C. Roelants5 · I. Testard6 · N. Cherradi7 · K. Lumniczky8 · S. Polozov4,9 · A. Napieralska3 · P. Widlak3 · U.S. Gaipl1 · C. Badie4 · J. Polanska2 · S. M. Candéias6 Received: 12 February 2020 / Accepted: 12 May 2020 © The Author(s) 2020
Abstract Background In this exploratory study, the impact of local irradiation on systemic changes in stress and immune parameters was investigated in eight patients treated with intensity-modulated radiation therapy (IMRT) or stereotactic ablative body radiotherapy (SABR) for prostate adenocarcinoma to gain deeper insights into how radiotherapy (RT) modulates the immune system. Patients and methods RT-qPCR, flow cytometry, metabolomics, and antibody arrays were used to monitor a panel of stress- and immune-related parameters before RT, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and 3 weeks later in the blood of IMRT (N = 4) or SABR (N = 4) patients. Effect size analysis was used for comparison of results at different timepoints. Results Several parameters were found to be differentially modulated in IMRT and SABR patients: the expression of TGFB1, IL1B, and CCL3 genes; the expression of HLA-DR on circulating monocytes; the abundance and ratio of phosphatidylcholine and lysophosphatidylcholine metabolites in plasma. More immune modulators in plasma were modulated during IMRT than SABR, with only two common proteins, namely GDF-15 and Tim-3. Conclusion Locally delivered RT induces systemic modulation of the immune system in prostate adenocarcinoma patients. IMRT and SABR appear to specifically affect distinct immune components.
Keywords Ionizing radiation · Biomarkers of radiation exposure · Prostate cancer · Systemic immune modulation · Immunophenotyping
B. Frey and J. Mika contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00066-020-01637-5) contains supplementary material, which is available to authorized users.
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Centre for Radiation, Chemical and Environmental Hazards, Cancers Mechanisms and Biomarkers group, Public Health England, Chilton, Didcot, OX11 ORQ, Oxfordshire, UK
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Inovarion, 75005 Paris, France
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Univ. Grenoble Alpes, CEA, CNRS, IRIG-LCBM-UMR5249, 38054 Grenoble, France
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Univ. Grenoble Alpes, INSERM, CEA, IRIG-BCI-UMR_S1036, 38054 Grenoble, France
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National Public Health Center, 1097 Budapest, Hungary
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HQ Science Limited, 5 The Quay, PE27 5AR St. Ives, Cambridgeshire, United Kingdom
S. M. Candéias
[email protected] 1
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Department of Radiation Oncology, Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, 91054 Erlangen, Bavaria, Germany Department of Data Science and Engineering, Silesian University of Technology, 44-100 Gliwice,
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