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

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.

Oligometastatic head and neck cancer: Which patients benefit from radical local treatment of all tumour sites?

“…While patients in the present series were largely treated before the current era of checkpoint inhibitors, advances in immunotherapies are an important consideration for future studies on oligometastatic head and neck cancer. As synergistic effects for the combination of radiotherapy and checkpoint inhibitor treatment have been described [20][21][22], the synthesis of local treatment and systemic immunotherapy could be especially beneficial in the oligometastatic setting. Ongoing trails like IMPORTANCE (NCT03386357) and CheckRad-CD8 (NCT03426657) are already investigating optimal combination strategies of radiotherapy and checkpoint inhibitor treatment and results are eagerly awaited.…”

Radiotherapy and the immune system: More than just immune suppression

“…The reason is probably the more ambivalent nature of RT in terms of modulation of the immune system. Independent of that, systemic alterations in immune and stress parameters are more and more observed after local application of RT 24 …”

Low dose ionizing radiation effects on the immune system

“…As previously mentioned, RT can induce long lasting systemic changes in immune/inflammatory parameters ( Marconi et al, 2019 ). These changes may appear gradually during the course of the treatment ( Manning et al, 2017 ), and even further evolve in the weeks following its completion ( Balazs et al, 2019 ; Frey et al, 2020 ). Hence, the modulation of the expression of some inflammatory ( ARG1, BCL2L1, MYC ) genes in blood cells was not apparent after the first two fractions but became significant after the 25th in patients treated for endometrial cancer.…”

“…The presence of a carcinoma in the head and neck area have indeed been shown to promote an immunosuppressive state in patients, which is even accentuated (increase in Tregs, increased expression of checkpoint molecules on CD4+ T cells), during and after RT ( Balazs et al, 2019 ). Systemic modulation of cellular and humoral immune parameters can also depend on the mode of radiation delivery ( Frey et al, 2020 ). However, most of these studies addressed changes occurring after repeated localized exposure, and it is therefore difficult to assess the exact role of low dose in these observations.…”