S2548
Radiobiology - Microenvironment
ESTRO 2026
expression and presented as Z-scores by subtracting the row median and dividing by the row standard deviation. Conclusion: Our findings suggest that tumour hypoxia and subtype transitions affect NAC response in MIBC. The shift from luminal to immune-infiltrated subtypes among non-responders, with significant high CD8 ⁺ T-cell infiltration and immune suppression, indicates an ineffective immune response in NAC non-responders. Luminal tumours with low hypoxia and no significant changes in CD8+ T-cells are more likely to achieve partial or complete response. These results highlight key determinants of NAC efficacy to guide treatment selection and intensification for poor-prognosis patients. References: 1. Saginala, K. et al. (2020). Med. Sci. 8,11–25.2. Catto, J. W. F. et al. (2023). BJU Int. 131,734–744.3. Kotwal, S. et al. (2008). Int J Radiat Oncol Biol Phys., 1;70(2):456- 63.4. Smith, V. et al. (2023). Int J Mol Sci. 18;24(10):8956. 5. Created in BioRender. Shamim, A.
Figure 1 – Study design, depicting the selection and processing of FFPE tumour samples.5 Results: Pre- and post-NAC, tumour subtypes identified as stroma-rich or basal/squamous were associated with higher hypoxia scores and T-stage than the luminal subtype. Partial responders exclusively exhibited luminal subtypes, while six non-responders transitioned from luminal to immune-infiltrated subtypes post-NAC. We identified eight immune-hot non-responders characterised by elevated CD8 ⁺ T-cell infiltration and high scores in stimulatory and suppressive immune signatures while there is no significant association found between CD8+ T-cell scores and immune-suppressive signatures in partial and complete responders (Figure 2).
(2026) https://BioRender.com/bhbk18v Keywords: MIBC, Hypoxia, Chemotherapy
Poster Discussion 2325
Myeloid–Endothelial Crosstalk Shapes Resistance to Chemoradiotherapy plus Immunotherapy in Cervical Cancer Yuanjie Cao, Jie Chen, Zhiyong Yuan Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China Purpose/Objective: Concurrent chemoradiotherapy (CCRT) combined with immune checkpoint inhibition (ICI) has emerged as a promising strategy for locally advanced cervical cancer (LACC). However, nearly one-third of patients fail to achieve complete response (CR), suggesting intrinsic resistance. The biological basis of such resistance— especially the interplay between immune and stromal compartments—remains unclear.To dissect transcriptomic and single-cell features associated with non-response to CCRT + ICI, and to identify microenvironmental networks that may drive immune evasion and treatment failure. Material/Methods: Pretreatment biopsies from 71 LACC patients treated
Figure 2 – The tumour immune signature scores before and after treatment with NAC. Each column represents a patient, divided by implied response to NAC into three groups of non, partial and complete responders. Each row represents an immune signature, with pre-NAC signature scores and post- NAC scores. The immune signature scores were calculated as the mean of the signature gene
with definitive CCRT plus the PD-1 inhibitor toripalimab were subjected to bulk RNA-seq.
Differential gene expression, Gene Ontology (GO), and gene set enrichment analysis (GSEA) were performed using DESeq2. Immune-cell composition was inferred by CIBERSORT and ESTIMATE algorithms. A prognostic model was developed by LASSO-Cox regression and
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