S2553
Radiobiology - Microenvironment
ESTRO 2026
Digital Poster 3719 Exploring MIBC cell survival and response to radiotherapy in self-assembling peptide hydrogels. Ellen E Slay 1,2 , Eve Tipple 2 , Conrado Guerrero Quiles 1 , Luisa Vanesa Biolatti 1 , Olga Tsigkou 2 , Julie Gough 2 , Peter J Hoskin 1,3 , Ananya Choudhury 1,3 1 Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. 2 Department of Materials, University of Manchester, Manchester, United Kingdom. 3 The Christie NHS Foundation Trust, Mount Vernon Cancer Center, Manchester, United Kingdom Purpose/Objective: Radiotherapy (RT) is a cornerstone treatment for muscle-invasive bladder cancer (MIBC), providing overall survival outcomes comparable to radical cystectomy (21% at 5 years [1]) while offering improved quality of life with bladder preservation. However, radioresistance is major clinical challenge, affecting one-third of patients [2]. Conventional 2D culture systems fail to capture the complexity of the tumour microenvironment (TME), particularly the extracellular matrix (ECM) stiffness. Increased matrix stiffness is associated with higher levels of radioresistance in 2D [3]. This study investigates MIBC cell survival and RT sensitivity within biomimetic 3D self-assembling peptide hydrogels (SAPHs), designed to recapitulate the physical and structural cues of the bladder TME. Material/Methods: MIBC cell lines (T24, J82, UMUC3) were embedded in SAPHs of increasing stiffness (0.7–1.3kPa, 3–5kPa, 6– 8kPa) to mimic cancer progression. Cell viability was assessed at day 14 using the LIVE/DEAD™ viability/cytotoxicity assay and 3D z-stack imaging (1000 μ m). Dose-response curves were generated following single-fraction RT exposures (0–10Gy) using an Xstrahl CIX3 irradiator. Results: All MIBC lines demonstrated sustained viability within the hydrogels over 14 days, confirming the suitability of the 3D system for long-term culture (Figure 1).
Conclusion: We have demonstrated a relationship between intratumoural microbial composition, HPV status and immune cell infiltration in a large cohort of patients treated in PLATO. Correlation of the intraumoural microbiota with longer term outcomes is warranted. References: [1] Upadhyay R, Dhakal A, Wheeler C, et al. Comparative analysis of the tumor microbiome, molecular profiles, and immune cell abundances by HPV status in mucosal head and neck cancers and their impact on survival. Cancer Biol Ther 2024;25:2350249.[2] Colbert LE, Alam MBE, Wang R, et al. Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring. Cancer Cell 2023;41:1945- 1962.e11. [3] Wakeham K, Murray L, Muirhead R, et al. Multicentre Investigation of Prognostic Factors Incorporating p16 and Tumour Infiltrating Lymphocytes for Anal Cancer After Chemoradiotherapy. Clin Oncol 2021;33:638–49. Keywords: Anal cancer, Intratumoural microbiota
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