S2571
Radiobiology – Normal tissue radiobiology
ESTRO 2026
Material/Methods: Transcriptomic analysis were performed on mouse oral mucosa following various injury models (acetic acid, 5-FU, mechanical damage, and 8 Gy × 3 irradiation). Single-cell RNA sequencing (scRNA-seq) of murine oral tissues (0 Gy vs. 8 Gy × 3) was employed to delineate the decisive role of epithelial cells in RIOM pathogenesis. In vitro, the effects of radiation on p53 expression and transcriptional activity were assessed in human oral keratinocytes (HOK) and human oral mucosal organoid (hOMo) by using molecular biology techniques. The impact of p53 on cellular radiosensitivity was further verified using specific p53 inhibitors. Finally, p53-knockout (p53-KO) mice were subjected to the RIOM model, and the role of p53 was definitively established through histopathological evaluation, analysis of inflammatory cell infiltration, and quantification of cytokine levels. Results: In contrast to oral ulcers induced by mechanical injury, chemotherapy, or acetic acid, radiation triggered a significant and specific activation of the p53 signaling pathway (NES=2.16, P<0.001) in the oral mucosa, characterized by upregulated expression of genes including Nkx2-9, Robo3, and IL24. Following an 8 Gy × 3 fractionated irradiation, the palatal and buccal mucosa exhibited a remodeled immune landscape with a decreased proportion of B, T, and NK cells and an increased infiltration of myeloid cells. Furthermore, epithelial cells demonstrated a robust upregulation of p53 target genes, including GDF15, IL1, and ACOD1, concomitant with the activation of the neutrophil extracellular trap (NETosis) pathway and enhanced epithelial-neutrophil communication. Ionizing radiation dose-dependently increased p53 expression and its transcriptional activity. Inhibition of p53 transcription with PFT α exacerbated cell death in irradiated human oral keratinocytes and reduced proliferation in oral mucosal organoids. Notably, p53- knockout mice displayed a dysregulated inflammatory response post-irradiation, with elevated levels of IL-24 and TNF- α , decreased levels of IL-6 and IL-1 β , and a significant increase in apoptosis in tongue tissue compared to wild-type controls. Conclusion: Collectively, our results establish that p53 activation is a central protective mechanism in radiation-induced oral mucositis. It modulates the local immune microenvironment by shifting leukocyte populations and enhancing epithelial-neutrophil crosstalk, and critically promotes cell survival and proliferation to limit tissue damage. The dysregulated inflammatory cytokine profile and exacerbated apoptosis in p53- deficient mice underscore the pivotal role of p53 in maintaining tissue homeostasis and mitigating the severity of oral mucosal injury following ionizing radiation.
Figure 2: Average number of γ H2AX foci (A) and pATM foci (B) for control, LD and HD skin fibroblasts (**: p < 0.01; ***: p < 0.001; NS: no significance). Conclusion: Previous irradiation induces persistent cellular alterations, including increased genomic instability, impaired DSB signaling, and defective DSB repair in primary ovine lung and skin fibroblasts. Keywords: pediatric cancer; radiosensitivity; DNA repair
Digital Poster 2268
Tumor suppressor p53 confers a protective role in radiation-induced oral mucositis by orchestrating
the epithelial-immune niche Shun Lu, Xin Wu, Fenghao Geng
Precision Radiation in Oncology Key Laboratory of Sichuan Province, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, China Purpose/Objective: To investigate the precise role of tumor suppressor p53 and mechanism in modulating the radiosensitivity of oral mucosal epithelium, thereby influencing the development and severity of Radiotherapy-induced oral mucositis (RIOM).
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