S2585
Radiobiology – Normal tissue radiobiology
ESTRO 2026
genes in 17Gy irradiated samples over the progression of the fibrosis, culminating in 5 months timepoint, where the lungs are fully fibrotic. On the contrary,10 Gy irradiated lungs show elevated levels of senescence associated molecules until 3 months after the irradiation, before decreasing close to NI levels.Molecular characterization of the senescent cells revealed upregulation of various pathways coherent with the literature: increase of p53 and p21 target genes, cytoskeleton remodelling and production of growth factors. We however failed to observed inflammation related molecules. Conclusion: We demonstrated the existence of a subtype of senescent aCap cells during RIPF, 5 months after 17Gy thoracic irradiation. The molecular markers of this senescent state are similar to already described endothelial senescence5, confirming the phenomenon at play. Targeting and removing this senescent subset is an interesting therapeutic target that could prove of great help to improve the treatment of RIPF. References: 1. Curras-Alonso S, Fouillade C et al.An interactive murine single-cell atlas of the lung responses to radiation injury. Nature communications, 14(1), 2445 (2023).2. Schafer, M., White, T., Iijima, K. et al. Cellular senescence mediates fibrotic pulmonary disease. Nature communications, 8, 14532 (2017). 3. Fouillade C, Favaudon V et al. FLASH Irradiation Spares Lung Progenitor Cells and Limits the Incidence of Radio-induced Senescence. Clin Cancer Res. 15;26(6):1497-1506 (2020).4. Gillich, A., Zhang, F., Farmer, C.G. et al. Capillary cell-type specialization in the alveolus. Nature 586, 785–789 (2020).5. Bochenek M, Schütz E, Schäfer K, Endothelial cell senescence and thrombosis: Ageing clots. Thrombosis Research, 147,36-45 (2016). Keywords: Lung, Fibrosis, Senescence Evaluation of the Effect of Anti-Interleukin-6 Receptor Antibodies on Radiation-Induced Lung Injury in a Murine Model Merve Duman 1 , Pinar Bulutay 2 , Duygu Sezen 1 , Altar Ozbiyik 3 , Ahmet Cingoz 4 , Nilhan Coskun 5 , Volkan Adsay 2 , Caglayan Selenge Beduk Esen 6 , Sukran Senyurek 1 , Nulifer Kilic Durankus 1 , Yasemin Atagun 1 , Ugur Selek 1 1 Radiation Oncology, Koç University School of Medicine, Istanbul, Turkey. 2 Pathology, Koç University School of Medicine, Istanbul, Turkey. 3 Molecular Biology and Genetics, Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey. 4 Molecular Biology, Bezmialem Vakıf University Institute of Life Sciences and Biotechnology, Istanbul, Digital Poster Highlight 4749
aged hematopoietic stem cells in mice. Nature medicine, 2016. 22(1): p. 78-83.4. Tran, A.P., et al., Long-term p21 and p53 dynamics regulate the frequency of mitosis events and cell cycle arrest following radiation damage. Cell Death Differ, 2023. 30(3): p. 660-672. Keywords: Salivary glands, Cell senescence, Senolytics Proffered Paper 4727 Senescence in capillary endothelial cells is concomitant to development of Radiation Induced Pulmonary Fibrosis Hugo JBP Laporte 1,2 , Sandra Curras Alonso 3 , Maxime Dubail 1 , Juliette Soulier 1 , Sophie Heinrich 1 , Charles Fouillade 1 , Arturo Londoño Vallejo 1 1 Université Paris-Saclay, Institut Curie, Paris, France. 2 UDE, Institut für Zellbiologie, Essen, Germany. 3 PSL, Institut Curie, Paris, France Purpose/Objective: Radiotherapy is one of the main therapeutic options for cancer patients but is limited by the damage inflicted on the surrounding healthy tissue. Radiation triggers an acute lung inflammation that may, sometimes, become chronic, fostering the development of acute pneumonitis or radiation- induced pulmonary fibrosis (RIPF)1. Lung fibrosis – both idiopathic (IPF) and radiation-induced – has been linked with senescence2,3, a cell state characterized by cell cycle arrest and a secretive phenotype (SASP). While the phenomenon is extensively described in IPF, cellular and molecular precision are still lacking for RIPF. Identifying senescent cells, and the associated SASP, would be of great interest in understanding
RIPF's pathogenicity. Material/Methods:
Our team generated scRNAseq data from classical C57BL/6J mouse models of radiation toxicities (17Gy thorax IR induces pulmonary fibrosis 4-5 months later; 10Gy thorax IR induces acute toxicities until 3 months, before regeneration) - an established mouse model of RIPF that allows time series study and recapitulates the disease progression in humans. Results: Single cell RNA sequencing on irradiated samples enabled us to identify all the key cell populations in the lung, and their variation during the development of the RIPF.We discovered that aerocytes (aCap), a subtype of capillary endothelial cells involved in gas exchanges4, are showing high levels of senescence 5 months after the 17Gy irradiation, when compared both to NI and 10 Gy lungs, notably through the expression of p16 and Serpine1, characteristic of senescence and SASP, respectively. Months by months analysis revealed gradual increase of SASP related
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