Systemic modulation of stress and immune parameters in patients treated for prostate adenocarcinoma by intensity-modulated radiation therapy or stereotactic ablative body radiotherapy

Strahlenther Onkol. 2020 Nov;196(11):1018-1033. doi: 10.1007/s00066-020-01637-5. Epub 2020 Jun 9.

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: Biomarkers of radiation exposure; Immunophenotyping; Ionizing radiation; Prostate cancer; Systemic immune modulation.

Publication types

  • Comparative Study

MeSH terms

  • Adenocarcinoma / immunology
  • Adenocarcinoma / physiopathology
  • Adenocarcinoma / radiotherapy*
  • Adenocarcinoma / surgery*
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Cytokines / blood
  • Gene Expression Regulation, Neoplastic / radiation effects
  • HLA Antigens / blood
  • Humans
  • Immune System / radiation effects*
  • Inflammation Mediators / blood
  • Lysophosphatidylcholines / blood
  • Male
  • Metabolome / radiation effects*
  • Middle Aged
  • Monocytes / immunology
  • Neoplasm Proteins / blood*
  • Phosphatidylcholines / blood
  • Prostatic Neoplasms / immunology
  • Prostatic Neoplasms / physiopathology
  • Prostatic Neoplasms / radiotherapy*
  • Prostatic Neoplasms / surgery*
  • Proteome / radiation effects*
  • Radiosurgery / methods*
  • Radiotherapy, Intensity-Modulated / methods*
  • Stress, Physiological / radiation effects*

Substances

  • Biomarkers
  • Cytokines
  • HLA Antigens
  • Inflammation Mediators
  • Lysophosphatidylcholines
  • Neoplasm Proteins
  • Phosphatidylcholines
  • Proteome