Radiotherapy plays a central role in cancer management, as approximately half of all patients receive it at some point during their disease. Its goal is to destroy tumor cells while sparing the surrounding healthy tissue as much as possible. Two techniques allow more precise targeting of the tumor volume: intensity-modulated radiation therapy (IMRT), delivered with conventional fractionation (e.g., 2 Gy per session, five days per week), and stereotactic ablative radiotherapy (SABR), which is hypofractionated (e.g., 7.25 Gy per session, five sessions spaced one day apart). Beyond their local effect, these irradiations exert systemic effects on the immune system that remain incompletely understood. It is this question that the study presented here addresses.
The authors followed eight patients with prostate adenocarcinoma, divided into two groups treated with IMRT (N = 4) and SABR (N = 4), respectively. A panel of stress- and immunity-related parameters was monitored in the blood at several key time points: before radiotherapy, after the first fraction (SABR) or the first week of treatment (IMRT), after the last fraction, and then three weeks later. Several approaches were combined: RT-qPCR for gene expression, flow cytometry, metabolomics, and antibody arrays. The analysis relied on the calculation of effect sizes to compare the different time points.
The results reveal distinct modulations depending on the treatment modality. Induction of IL1B and TGFB1 gene transcription was observed only in patients treated with IMRT, who also displayed modulation of a substantially greater number of cytokines and serum proteins than patients receiving SABR. The change in the lysophosphatidylcholine/phosphatidylcholine (LPC/PC) ratio, a metabolomic indicator of inflammation, also differed markedly between the two protocols. Conversely, certain markers of cell activation changed uniformly across all patients: an increase in the proportion of PD-1-expressing CD4+ T cells was thus observed at the end of treatment. Among the plasma proteins, only two were shared by both groups, GDF-15 and Tim-3, but their regulation occurred in opposite directions depending on the modality. The authors also note a regulation of factors related to endothelial dysfunction and tissue remodeling in IMRT patients only.
The authors conclude that localized irradiation induces a systemic modulation of a wide range of cellular and humoral immune parameters, and that modalities with comparable therapeutic efficacy and toxicity can differently affect immune homeostasis, up to five weeks after the end of treatment. As this is an exploratory study conducted on a small sample, these observations will need to be confirmed in larger cohorts and at later time points.