ESTRO 2025 - Abstract Book

S3873

Radiobiology - Immuno-radiobiology

ESTRO 2025

572

Proffered Paper Spatiotemporally deciphering the response dynamics of micro-satellite stable rectal cancer to neoadjuvant short-course radiotherapy and PD-1 blockade Jingwen Wang, Zhen Zhang Department of radiation oncology, Fudan University Shanghai Cancer Center, Shanghai, China Purpose/Objective: Neoadjuvant chemoradiotherapy is the stand of care for patients with locally advanced rectal cancer (LARC). For microsatellite-stable (MSS) LARC patients, combining immune checkpoint inhibitors (ICIs) with radiotherapy has shown improved tumor regression in a prospective phase II trial (TORCH, NCT04518280), though the mechanisms behind tumor response remain unclear. Material/Methods: We prospectively collected 60 pre-, mid- and post-treatment tumor samples from 39 LARC patients in the TORCH clinical trial, utilizing single-cell sequencing and spatial transcriptomics to explore cell dynamics and their association with therapeutic efficacy. Results: In well responders, combination therapy expanded the CD8 + and CD4 + memory T cell pool, which interacted with type 2 dendritic cells and clustered around non-malignant epithelial cells, forming part of tertiary lymphoid structures, as validated by spatial transcriptomics. In poor responders, the tumor microenvironment was enriched with immunosuppressive cells clustering around cancer-associated fibroblasts. Conclusion: This study uncovers mechanisms underlying the efficacy of radiotherapy combined with ICIs and provides valuable resources for identifying targets in MSS LARC patients. Digital Poster Decoding Radiotherapy Resistance: The Crucial Role of Macrophages in Triple Negative Breast Cancer Ana C Borges 1,2,3 , Lisa Bouarroudj 4 , Ângela M Magalhães 2,3 , Joana Paredes 5 , Michele Mondini 4 , Eric Deutsch 4 , Flávia Castro 2 , Maria J Oliveira 2 1 U1030, Gustave Roussy, Paris, France. 2 Tumour and Microenvironment Interactions Group, i3S, Porto, Portugal. 3 BiotechHealth, ICBAS, Porto, Portugal. 4 Inserm 1030, Gustave Roussy, Paris, France. 5 Cancer Metastasis, i3S, Porto, Portugal Purpose/Objective: Triple-negative breast cancer (TNBC), the most aggressive subtype, is associated with higher risk of relapse following radiotherapy (RT) 1 . To overcome this clinical challenge, focus must be paid to immune cells, in particular macrophages, highly recruited upon RT, and associated with tumor progression and recurrence 2,3 . Material/Methods: Herein, we established and characterized 3D spheroids, gathering TNBC cells (tumor spheroids, TS) or TNBC cells with human macrophages (tumor immune spheroids, TiS). These were then submitted to five cumulative fractions of Keywords: MSS rectal cancer, clinical trial 892