S2612
Radiobiology - Translational radiobiology
ESTRO 2026
Conclusion: Gut microbiota enriched in SCFA-producing taxa is associated with favourable CRT response in NPC and CC patients. In vivo, SCFA administration enhanced tumour control when combined with irradiation and was associated with a reduction in systemic and intratumoural Tregs. To the best of our knowledge, this represents the first in vivo evidence linking SCFA treatment with reduced Treg levels and improved radiotherapy efficacy. These findings highlight the translational potential of microbiota-targeted or SCFA- based strategies to improve CRT outcomes. References: 1. Routy B et al. Science 2018;359:91–97.2. Roy S et al. Nat Commun 2023;14:3570.3. Then C-K et al. Gut Microbes 2024;16(1):2258703. Keywords: Gut microbiota, chemoradiotherapy, Treg cells Digital Poster 652 Development and validation of a 20-gene pan- cancer hypoxia signature for prognostic stratification across multiple solid tumours Abdelrahman Masheh 1 , Ahmed Salem 2 , Fatima Farhan 3,1 , Badie Abuzaid 1 , Lina Al-Zerikat 1 , Mohammad Akash 1 1 Faculty of Medicine, The Hashemite University, Zarqa, Jordan. 2 Department of Anatomy, Physiology and Biochemistry, Faculty of Medicine, The Hashemite University, Zarqa, Jordan. 3 Clinical Bioinformatician, Bionl, MA, USA Purpose/Objective: Tumour hypoxia is a driver of progression, immune evasion, and radio-resistance across solid malignancies1. While cancer-specific hypoxia gene signatures exist, a validated signature applicable across tumour types is lacking. We aimed to develop and validate a pan-cancer hypoxia gene signature capable of improving prognostic stratification across multiple tumour sites. Material/Methods: RNA-sequencing and clinical data from TCGA lung adenocarcinoma/squamous carcinoma (LUAD/LUSC), head and neck squamous cell carcinoma (HNSC), and pancreatic adenocarcinoma (PAAD) cohorts were analysed. Each dataset was randomly partitioned into training (70%) and validation (30%) subsets. In each cohort, patients were dichotomised using hypoxia scores derived from established tumour-specific signatures2–4. Cancer type-specific differential expression analyses (adjusted P<0.05; log ₂ FC>1) were undertaken to identify consistently upregulated hypoxia-associated genes. A pan-cancer hypoxia gene signature was generated by aggregating overlapping
1 Department of Radiation Oncology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan. 2 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 3 International Master/Ph.D. Program in Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 4 Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan Purpose/Objective: Inter-individual variation in chemoradiotherapy (CRT) response remains a major clinical challenge, influenced by tumour heterogeneity, immune suppression, and host–microbiome interactions. Emerging evidence suggests that gut microbial metabolites, particularly short-chain fatty acids (SCFAs), modulate systemic immunity and tumour radiosensitivity. This study aimed to (i) characterise gut microbiota composition in nasopharyngeal carcinoma (NPC) and cervical cancer (CC) patients undergoing CRT, (ii) identify microbial taxa associated with treatment response, and (iii) evaluate whether SCFAs enhance tumour control and alter immune profiles when combined with irradiation (IR) in vivo. Material/Methods: Newly diagnosed, treatment-naïve NPC and CC patients were prospectively recruited. Clinical, lifestyle, and dietary data were collected. Faecal samples were obtained before and after CRT using OMNIgene GUT kits and analysed by full-length 16S rRNA sequencing (Oxford Nanopore GridION). Tumour response was evaluated by MRI or CT at 3–6 month intervals. For mechanistic studies, C57BL/6 mice bearing MOC2 oral carcinoma xenografts received SCFA supplementation, IR, or combined SCFA + IR treatment. Flow cytometry was performed on spleen and tumour tissues to quantify systemic and intratumoural regulatory T cells (Tregs). Results: Across patients, dominant taxa included Klebsiella pneumoniae, Escherichia coli, Faecalibacterium prausnitzii, Bacteroides vulgatus, and Bacteroides plebeius. In CC (n = 7), complete responders (CR, n = 3) exhibited higher Peptostreptococcus abundance than partial responders (PR). In NPC (n = 7), CRs were enriched in SCFA-producing genera (Blautia, Lachnospira, Anaerobutyricum) compared with PRs (44.2 % vs 25.1 %, p = 0.024). Functional pathway prediction indicated increased β -galactosidase activity, consistent with enhanced SCFA biosynthetic potential in CRs. In vivo, SCFA supplementation combined with IR significantly improved tumour control relative to IR alone. Both spleen and tumour tissues from SCFA- treated mice showed reduced Treg populations, suggesting immunomodulatory effects associated with enhanced tumour response.
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