S2564
Radiobiology – Normal tissue radiobiology
ESTRO 2026
or Wnt depletion. Results:
Proffered Paper 1774 Tissue-adapted Tregs harness inflammatory signals to promote intestinal repair from therapy- related injury Julius C Fischer 1 , Sascha Goettert 2 , Maximilian Giller 1 , Paul Heinrich 2 , Kaiji Fan 2 , Omer Khalid 2 , Caroline N Walther 1 , Maria Drießlein 2 , Sophie M Nefzger 1 , Gabriel Eisenkolb 3 , Vincent R Timnik 1 , Sebastian Jarosch 4 , Sarah Diederich 1 , Nicole A Schmid 1 , Katja Steiger 5 , Michael Rehli 2 , Markus Tschurtschenthaler 6 , Stephanie E. Combs 1 , Dirk H Busch 4 , Ernst Holler 2 , Simon Heidegger 3 , Hendrik Poeck 2 1 Radiation Oncology, Technical University of Munich, Munich, Germany. 2 Department for Internal Medicine III, University Hospital Regensburg, Regensburg, Germany. 3 Internal Medicine III, Technical University of Munich, Munich, Germany. 4 Medical Microbiology, Immunology and Hygiene, Technical University of Munich, Munich, Germany. 5 Institut of Pathology, Technical University of Munich, Munich, Germany. 6 Center for Translational Cancer Research (TranslaTUM), Technical University of Munich, Munich, Germany Purpose/Objective: Therapy-induced intestinal injury remains a major dose-limiting toxicity in oncology, particularly in radiation therapy. The intestinal stem cell compartment plays a central role in epithelial regeneration but is highly sensitive to stress and immune-mediated cytotoxicity, especially through interferon γ (IFN γ ). This study aimed to advance our understanding of how intestinal immune cells contribute to epithelial regeneration following intestinal injury, with the goal of identifying new therapeutic strategies to enhance repair. Material/Methods: Murine models of abdominal irradiation (ABI) or total body irradiation followed by allogeneic bone marrow transplantation (allo-BMT) were used to study intestinal injury and regeneration. Epithelial regeneration was assessed by weight recovery, intestinal permeability (FITC–dextran assay), and ex vivo organoid formation. T-cell subsets were characterized using flow cytometry, immunohistochemistry of murine samples, and single- cell RNA sequencing (scRNA-seq) and chip cytometry of human samples. Murine and patient-derived intestinal organoids were co-cultured with defined T- cell subsets or stimulated with recombinant cytokines, with or without irradiation. Organoids subjected to T- cell co-culture or cytokine stimulation were analyzed by scRNA-seq. Functional validation of identified targets was performed using pharmacological inhibition. Growth factor substitution experiments tested the ability of cytokines to compensate for EGF
Unexpectedly, in both allo-BMT and ABI models, enhanced intestinal T-cell infiltration and IFN γ expression correlated not only with the extent of epithelial injury but also with subsequent regeneration. IFN γ -deficient mice exhibited impaired recovery, reduced epithelial integrity, and diminished organoid regeneration. The degree of tissue damage correlated with enhanced infiltration of Treg cells. Treg cells within damaged intestinal tissue expressed IFN γ and IL-10, and their co-culture with organoids enhanced epithelial growth in an IFN γ receptor– and IL-10–dependent manner. Combined IFN γ and IL-10 stimulation, but not either cytokine alone, restored organoid growth after irradiation and promoted epithelial regeneration following ABI. scRNA-seq revealed activation of mTORC1 and Myc pathways in ISCs following combined cytokine stimulation or Treg co-culture, driving epithelial repair. Functionally, IFN γ compensated for EGF depletion by promoting proliferation, whereas IL-10 preserved the ISC pool via Wnt-like activity. Only their combination sustained long-term epithelial growth and regeneration. Pharmacological inhibition of mTORC1 or Myc abrogated these effects. Conclusion: Tissue-adapted Treg cells coordinate epithelial repair after radiation- and immune–mediated intestinal injury through combined IFN γ and IL-10 signaling. This dual pathway activates mTORC1/Myc-driven proliferation while maintaining ISC integrity, revealing a regenerative role of inflammatory signaling. Targeting this mechanism offers novel therapeutic opportunities to enhance intestinal recovery following cancer therapy. Keywords: Regulatory T cells;Intestinal toxicity;stem cells A Novel Nebulized Nanoherbal System for Preventing Radiation-Induced Lung Injury via Ferroptosis Suppression Meihua Chen 1 , Li Quan 1 , Jinyi Lang 2 1 Department of Radiation Oncology, Sichuan Cancer Hospital ＆ Institute, Chengdu, China. 2 Department of Radiation Oncology, Sichuan Cancer Hospital & Institute, Chengdu, China Purpose/Objective: Radiation-induced lung injury (RILI) remains a dose- limiting complication of thoracic radiotherapy. The traditional Huaxian Formula (HXF) has shown potential in mitigating RILI, but its clinical application is limited by poor solubility and bioavailability. This study aimed Poster Discussion 1802
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