S2533
Radiobiology – Immuno-radiobiology
ESTRO 2026
Brussels, Belgium. 3 Department of Abdominal Transplantation, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 4 Department of Colorectal Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 6 Department of Pathology, Cliniques Universitaires Saint-Luc, Brussels, Belgium. 7 Department of Medical Oncology, Cliniques Universitaires Saint-Luc, Brussels, Belgium 5 Department of Thoracic Surgery, Cliniques Universitaires Saint-Luc, Brussels, Belgium. Purpose/Objective: Microsatellite stable colorectal cancer (MSS CRC) shows limited responsiveness to immunotherapy due to a tumour microenvironment poorly infiltrated by immune cells [1, 2]. Radiotherapy (RT) can elicit local and systemic immune activation and may thereby restore MSS CRC sensitivity to immunotherapy. While these effects have been demonstrated in preclinical models, translational evidence in humans remains limited, and early clinical trials combining RT with ICI in MSS CRC have yielded modest outcomes [3, 4]. This study investigated the immunomodulatory effects of hypofractionated RT on systemic and local immunity in MSS CRC. Material/Methods: Patients scheduled for surgical resection of primary or metastatic MSS CRC lesions were prospectively enrolled. The objective was to compare RT-induced immune responses according to RT dose and anatomical site. RT consisted of 3 × 8Gy delivered daily (Mod-RT) 4–8 days before surgery. In selected patients with multiple lesions, additional sites received 3 × 1– 2Gy (Low-RT) and/or were spared (Out-RT). Comparisons were also made with paired, never- irradiated lesions (No-RT) from a historical cohort. Tumour tissue and paired blood samples (pre-RT and post-RT) were collected. Peripheral blood mononuclear cells (PBMCs) were analysed by multiparametric flow cytometry (FACS) using panels assessing immune composition and T-cell activation/exhaustion markers. TCR-seq quantifies RT- induced changes in T-cell clonality. Plasma proteomics was performed by mass spectrometry. In tumours, multiplex immunofluorescence evaluated T-cell infiltration (CD3, CD8, CD45, PD-1). Bulk RNA-seq was performed on four matched Mod-RT and No-RT liver lesions. Results: Eighteen patients were included (3 primary tumours, 3 lung, 10 liver, and 2 primary + liver metastases). In blood, FACS revealed a post-RT enrichment of CD4 ⁺ terminally differentiated effector memory RA+ (TEMRA) T cells (p = 0.049). TCR-seq showed decreased Shannon diversity (p = 0.007) and increased clonal overrepresentation (p = 0.047). Proteomic identified enrichment of the p53 pathway after RT. Tumour
approach.
Conclusion: In this real-world study of patients with LA-NSCLC, the Neo-RD-chemo plus standard-dose immunotherapy, followed by CCRT and consolidative immunotherapy, yielded comparable survival outcomes to the Neo-SD- chemo plus standard-dose immunotherapy and was associated with a favorable safety profile. Keywords: LA-NSCLC, Neoadjuvant reduced-dose, CCRT Radiotherapy-driven immune remodeling in microsatellite-stable colorectal cancer: insights into systemic and tumour-level responses Julien Pierrard 1,2 , Elena Benidovskaya 1 , Aurélie Daumerie 1 , Davide Brusa 1 , Laurent Coubeau 3 , Lancelot Marique 3 , Radu Bachmann 4 , Christophe Remue 4 , Valérie Lacroix 5 , Catherine Hubert 3 , Pamela Baldin 6 , Marc Van den Eynde 7,1 , Geneviève Van Ooteghem 2 1 Institut de Recherche Experimentale et Clinique (IREC), UCLouvain, Brussels, Belgium. 2 Department of Radiation Oncology, Cliniques Universitaires Saint-Luc, Proffered Paper 2734
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