ESTRO 2025 - Abstract Book

S3896

Radiobiology - Microenvironment

ESTRO 2025

Keywords: low-dose-radiotherapy, TME, resistance mechanisms

References: Herrera, F. G. et al., 2022. Low-Dose Radiotherapy Reverses Tumor Immune Desertification and Resistance to Immunotherapy. Cancer Discov 12, 108-133. Andreatta, M., et al. J., 2021. Interpretation of T cell states from single-cell transcriptomics data using reference atlases. Nat Commun 12, 2965.

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Mini-Oral Effect of irradiation on Head and Neck Squamous Cell Carcinoma-derived CAF phenotype and function. Kris T.P.M. Raaijmakers 1 , Anne Beerkens 1 , Rens Peters 1 , Vera Mekers 1 , Maud Beekmans 1 , Willem L.J. Weijs 2 , Jimmie Honings 3 , Johannes H.A.M. Kaanders 1 , Gosse J. Adema 4 , Johan Bussink 4 , Marleen Ansems 4 1 Department of Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands. 2 Department of Oral and Maxillofacial Surgery and Head and Neck Surgery, Radboud University Medical Center, Nijmegen, Netherlands. 3 Department of Otorhinolaryngology and Head and Neck Surgery, Radboud University Medical Center, Nijmegen, Netherlands. 4 Radiation Oncology, Radboud University Medical Center, Nijmegen, Netherlands Purpose/Objective: Head and neck squamous cell carcinomas (HNSCC) is the most prevalent type of head and neck cancer, originating from the mucosal epithelium of the oral cavity, hypopharynx and larynx. Despite aggressive therapy, HNSCC is associated with a 5-year survival rate of less than 50%. The tumor microenvironment of late-stage HNSCC consists up to 80% of cancer-associated fibroblasts (CAFs). CAFs represent a heterogeneous group of cells that is actively involved in both tumor immunomodulation and matrix organization and have been ascribed both pro-tumorigenic and anti-tumorigenic properties. The majority of HNSCC patients is treated with radiotherapy. Notably, CAFs are particularly radioresistant, and are associated with the development of tumor radioresistance. Still, the exact effect of radiotherapy on CAFs in HNSCC remains elusive. In this study, we aim to characterize both the effect of radiotherapy on CAFs, as well as its possible consequences for the tumor microenvironment. Material/Methods: Primary HNSCC CAFs were isolated from resection material of multiple patients, cultured, and exposed to a single dose of ionizing radiation in the range of 0-18 Gy ex vivo. Phenotypic changes of CAFs upon irradiation were evaluated via several characterizing and functional assays. Results: We demonstrate that CAFs have a significant capability to survive irradiation, but that irradiation does reduce CAF proliferation. In agreement, we find that irradiation triggers CAF senescence. Using CAF-conditioned medium, we show that CAFs are able to enhance HNSCC cell migration and that they retain this property after irradiation (figure 1). In addition, we demonstrate that it is possible to selectively kill CAFs that have undergone radiation-induced senescence using senolytic drugs (figure 2).