ESTRO 2025 - Abstract Book

S3874

Radiobiology - Immuno-radiobiology

ESTRO 2025

2.67Gy or 5.2Gy, mimicking one week of TNBC patients treatment. Multiomic studies were further performed to unveil the mechanisms underlying macrophage-mediated TNBC radioresistance.

Results: Collected data indicates that RT selectively kills cancer cells while does not affect macrophage and cancer cells viability in TiS. Specifically, macrophages protected cancer cells from RT-induced cell death throughout time, potentiated their proliferation and modulated them to increase CD47 and CD40 expression, which may favor immune escape. Notably, RT seems to potentiate different macrophage polarization signatures over time, ranging from an anti-tumor pro inflammatory towards a more pro-tumor anti-inflammatory phenotype. RNASeq analysis identified CXCR2 as significantly increased in irradiated macrophages. Concordantly, Multiplex ELISA revealed an increased secretion of unexplored cytokines as IL8 (CXCR2 ligand), which may favor radioresistance, being correlated with a worst prognosis on a TNBC patients cohort. Furthermore, in the absence of macrophages, irradiated cancer cells upregulated pathways related to cell cycle arrest and DNA damage and exhibited an increase on lipid droplets and mitochondria deregulation. Contrarily, the most altered pathways on irradiated TiS were on sterol and cholesterol metabolic processes, highlighting a potentially novel radioresistance mechanism through which macrophages subvert and nourish the tumor microenvironment, modifying cancer cells lipid metabolism to escape RT-mediated cell death. Conclusion: Since these novel candidates correlate with poor prognosis in TNBC, targeting lipid metabolism will hopefully revert macrophage-mediated radioresistance, and sensitize cancer cells to death, improving RT response and patient prognosis. Keywords: macrophages, radioresistance, target therapy References: [1] Langlands FE, Horgan K, Dodwell DD, Smith L. (2013) Breast cancer subtypes: response to radiotherapy and potential radiosensitisation. Br J Radiol, 86(1023): p.20120601. Doi: 10.1259/bjr.20120601 [2] Tu D, Dou J, Wang M, Zhuang H, Zhang X. M2 macrophages contribute to cell proliferation and migration of breast cancer. Cell Biol Int. 2021 Apr;45(4):831-838. doi: 10.1002/cbin.11528. Epub 2021 Jan 13. PMID: 33325089. [3] McLaughlin, M., Patin, E.C., Pedersen, M. et al. Inflammatory microenvironment remodelling by tumour cells after radiotherapy. Nat Rev Cancer 20, 203–217 (2020). https://doi.org/10.1038/s41568-020-0246- Digital Poster Effect of combined conventional and mini beam radiation therapy on immune system response Federica Vurro 1 , Lisa Alborghetti 1,2 , Maria Assunta Lacavalla 1,3 , Macrina Milani Capialbi 1 , Stefano Pizzardi 1 , Claudio Fiorino 4 , Antonello Spinelli 1 1 Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy. 2 Engineering and Physics, University of Verona, Verona, Italy. 3 Department of chemical sciences, University of Padova, Padova, Italy. 4 Medical Physics Department, IRCCS San Raffaele Scientific Institute, Milan, Italy Purpose/Objective: Minibeam Radiation Therapy (MBRT) is a form of spatially fractionated radiation therapy that employs submillimetric radiation beams, creating dose distributions characterized by alternating high-dose regions (peaks) and low-dose regions (valleys). This dose modulation has the effect of increasing the radiation tolerance of healthy tissue. Recent data have shown that MBRT can activate distinct radiobiological mechanisms of action, in particular, T cells play a crucial role[1]. Unlike conventional radiotherapy (CONV), MBRT requires the optimization of different parameters, including peak dose, valley dose, and peak-to-valley dose ratio (PVDR), that may influence treatment outcomes[2]. The main goal of this project will be to evaluate the biological effects of the treatment with CONV, MBRT, and combined CONV and MBRT (MBRT-CONV). 1627