ESTRO 2025 - Abstract Book

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Invited Speaker

ESTRO 2025

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Speaker Abstracts Dissecting and rewiring myeloid cell heterogeneity in cancer: Understanding therapy-induced changes Leila Akkari Tumor Biology and Immunology, Netherlands cancer institute, amsterdam, Netherlands

Abstract: Tumors growing in metabolically-challenged environments are particularly reliant on cancer cells and immune cell metabolic cross-talk to satisfy their high metabolic needs. However, the intricacies of this metabolic interplay and the consequences on immune cell subsets diversity and function remain largely unexplored. We interrogated the heterogeneity of the tumor microenvironment using multi-omics analyses in preclinical brain cancer mouse models and patient datasets and identified metabolically-rewired tumor-associated macrophage (TAM), myeloid cells and regulatory T cell subpopulations fueling cancer progression and resistance to standard of care and immunotherapies. Our work reveal the dynamic evolution of specific immune cell compartment and resist to therapies, with potential for exploiting these vulnerabilities therapeutically.

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Speaker Abstracts Evaluating tumour microenvironment alterations pre- and post- radiation treatment Fernanda G Herrera Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland

Abstract: Our research has demonstrated that low-dose radiation therapy (LDRT, doses below the threshold to induce significant DNA damage, (i.e.,<1 Gy) can reprogram the TME, converting immunologically cold tumors into hot inflamed tumors that are more responsive to ICB [5]. Using the syngeneic ID8 mouse model of metastatic ovarian cancer, we developed a novel radio-immunotherapy regimen (RACIM), integrating: LDRT, ICB (anti-CTLA4 and anti PD1 to increase the priming and killing capacity of T cells), and Immune-modulating agents (CD40 agonist to increase the co-stimulatory capacity of antigen-presenting cells, and low-dose cyclophosphamide to deplete regulatory T cells). Our preclinical studies showed that RACIM significantly improved immune infiltration, tumor regression, and survival [5]. Translating these findings to clinical trials, the RACIN Phase I study (NCT03728179) demonstrated that LDRT could enhance ICB efficacy in patients with metastatic solid tumors, with a notable subset achieving durable responses — particularly those with homologous recombination-deficient tumors and G2/M cell cycle arrest signatures. These findings suggest that tumor-intrinsic factors, including DNA damage response pathways, influence patient outcomes and warrant further investigation.

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Speaker Abstracts Metabolic barriers to immunogenic radiotherapy response Erik Wennerberg Radiotherapy and Imaging, Institute of Cancer Research, London, United Kingdom