ESTRO 2025 - Abstract Book

S3887

Radiobiology - Immuno-radiobiology

ESTRO 2025

1β. Co-culture with bone marrow-derived dendritic cells (BMDCs) showed that irradiated treatment-sensitive tumor cells were more potent in inducing DC activation partially dependent on AIM2, as AIM2 knockdown reduced this effect. Lastly, we checked samples from rectal cancer patients and found higher expression of AIM2 in responders to neoadjuvant therapy compared to non-responders. Conclusion: Overall, we demonstrated that radiation-induced activation of the AIM2 inflammasome enhanced antitumor responses by triggering IL-1β signaling and subsequent DC activation. Targeting the AIM2-IL-1β axis may represent a therapeutic strategy to improve combined radiotherapy and immunotherapy in MSS CRC. References: 1. Chen, D., et al. Tumor Treating Fields dually activate STING and AIM2 inflammasomes to induce adjuvant immunity in glioblastoma. J Clin Invest, 2022. 132(8): e149258. 2. Han, C., et al. The AIM2 and NLRP3 inflammasomes trigger IL-1-mediated antitumor effects during radiation. Sci Immunol, 2021. 6(59): eabc6998. 3. Gray, E.E., et al. The AIM2-like Receptors Are Dispensable for the Interferon Response to Intracellular DNA. Immunity, 2016. 45(2): 255-66. 4. Xia, F., et al. Randomized Phase II Trial of Immunotherapy-Based Total Neoadjuvant Therapy for Proficient Mismatch Repair or Microsatellite Stable Locally Advanced Rectal Cancer (TORCH). J Clin Oncol, 2024. 42(28): 3308-3318. Keywords: colorectal cancer, AIM2 inflammasome Digital Poster The Impact of Stereotactic Body Radiotherapy on the Dynamics of Circulating Tumour DNA in Patients with Oligo-Progressive Disease Aisling Barry 1 , Scott Bratman 2 , Eric Zhao 2 , Jinfeng Zou 3 , Neelabh Rastogi 2 , Emma Hill 4 , Ekaterina Kalashnikova 4 , Philip Ye 5 , Rachel Glicksman 2 , Joelle Helou 6 1 Cancer Research@UCC, College of Medicine and Health, Cork, Ireland. 2 Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Canada. 3 University Health netqork, UHN, Toronto, Canada. 4 Natera, Natera inc, Austin, USA. 5 Department of Biostastics, Princess Margaret Cancer Centre, Toronto, Canada. 6 Department of Radiation Oncology, London Health Sciences, London, ON, Canada Purpose/Objective: Stereotactic Body Radiotherapy (SBRT) is increasingly used as an ablative treatment in patients with limited progressive metastatic disease (oligo-progression (OP)). Results from recent trials are controversial[1], suggesting an opportunity for better patient selection. Novel biomarkers such as circulating tumour DNA (ctDNA) may aid clinical decision making in this setting. Material/Methods: RADIANT[2], phase II prospective single institutional study of patients with OP (≤5 progressing metastatic lesions), treated with SBRT. We prospectively collected frozen plasma samples (3 – 4mL) and whole blood (Peripheral blood mononuclear cells or germline DNA – MTM/mL) at five timepoints (TP) – baseline (TP1), post fraction 1 of SBRT (TP2), post final fraction (TP3), 6-weeks (TP4) and 3-months post SBRT (TP5). Descriptive statistics were computed using SAS. 3875