ESTRO 2025 - Abstract Book

S4030

Radiobiology - Tumour radiobiology

ESTRO 2025

inflammatory cytokines such as TNFα, IL6 and IL1β [3] are thought to play a crucial role. Here, we investigated the release of these cytokines by “peak-dose” and “valley-dose” irradiated cells, in order to understand where these factors originate from, and compared the bystander response of CRT and MRT. Material/Methods: GL261 and SB28 murine glioblastoma cells were irradiated with increasing peak and valley CRT doses as well as MRT equivalent uniform doses (EUD) with a PVDR of 20. Conditioned medium from irradiated cells was transferred to non-irradiated cells at different time points (30 min, 6 h, 24 h). Clonogenic cell survival was used as an endpoint for analysis. In addition, inflammatory cytokines from the medium were quantified using a multiplexed immunoassay with the same doses and time points. Results: Conditioned medium from cells irradiated with MRT 8 Gy EUD caused a significant decrease in cell survival by 38% in bystander cells in comparison to only 13% from CRT 8 Gy (valley dose). Cells irradiated with 8 Gy (valley) released 15 times more IL6 within the first 6 hours post irradiation, while 160 Gy (peak) prolonged this effect for at least up to 24h post irradiation, suggesting the involvement of peak-derived IL6 in the observed survival reduction of bystander cells. Conclusion: These preliminary findings point towards a possible role of IL6 released by peak-irradiated cells in modulating bystander effects. We hypothesize that the activation of this response is a consequence of magnified activation of the cGAS-STING pathway in the peaks. Further experiments will aim at blocking IL6 in order to verify its role in MRT mediated bystander response. References: 1. Laissue, J. A et al., (1998). Neuropathology of ablation of rat gliosarcomas and contiguous brain tissues using a microplanar beam of synchrotron-wiggler-generated X rays. International Journal of Cancer, 78(5), 654–660. 2. Dilmanian, F et al., (2003). Murine EMT-6 carcinoma: High therapeutic efficacy of microbeam radiation therapy. Radiation Research, 159(5), 632–641. 3. Paluch-Ferszt, et al ., (2021). Radiation-Induced Bystander Effect Research: Literature review. Acta Physica Polonica A, 139(3), 266–272. Keywords: Microbeam radiotherapy, bystander effect, IL6