Publication Database

The potential of patient-derived organoids to recapitulate and model distinct radiosensitivity phenotypes in HNSCC (2025)

Art

Vortrag

Autoren

Fisch, A.-S. (WE 1)

Sachse, V.

Pestana, A.

Fähling, M.

Plendl, J. (WE 1)

Tinhofer, I.

Kongress

XXXVth Congress of the European Association of Veterinary Anatomists (EAVA)

Toulouse, 22. – 25.07.2025

Quelle

Anatomia, histologia, embryologia

Bandzählung: 54

Heftzählung: Suppl. 1

Seiten: e70056

ISSN: 0340-2096

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/epdf/10.1111/ahe.70056

DOI: 10.1111/ahe.70056

Kontakt

Institut für Veterinär-Anatomie

Koserstr. 20
14195 Berlin
+49 30 838 75784
anatomie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Head and neck squamous cell carcinomas (HNSCC) are commonly treated with radiotherapy, either alone or combined with surgery and chemotherapy. However, a substantial proportion of patients develop local recurrence following (chemo)radiation, often due to tumor-intrinsic resistance mechanisms such as hypoxia. Given the biological heterogeneity and patient-specific differences in radioresponse, there is a critical need for preclinical models that can capture this variability. This study investigates patient-derived organoids (PDOs) as individualized in vitro models to assess radiosensitivity and therapy resistance mechanisms.
Eight PDO models from our in-house biobank were exposed to increasing doses of x-ray irradiation (0, 2, 4, 6, 8 Gy). Metabolic activity was assessed using the CellTiter-Glo assay seven days post-irradiation. All models showed dose-dependent viability loss, but with marked interpatient variability. To model hypoxia-induced radioresistance, PDO line HN041 was cultured in Matrigel under either atmospheric or hypoxic (1% pO₂) conditions for four days, allowing organoid formation. Hypoxia induction was confirmed by positive pimonidazole staining. Organoids were then irradiated under hypoxic conditions using BD GasPak™ pouches and subsequently cultured under normoxia. Functional outcomes were assessed one week later by measuring organoid size and performing a clonogenic survival assay. Notably, non-irradiated organoids preconditioned under hypoxia yielded significantly higher total cell numbers compared to those cultured under normoxia (9.5×10⁶ vs. 7.2×10⁶ cells, p = 0.01), while organoid sizes were comparable (176 µm vs. 168 µm, p = 0.19), suggesting a proliferative advantage without structural changes. Clonogenic survival analysis revealed a significant increase in radio-resistance by hypoxic pre-treatment, with fitted D₀ values of 9.7 Gy (hypoxic preconditioning) versus 4.9 Gy (normoxia) (p = 0.002).
These findings demonstrate that PDOs recapitulate interpatient differences in radiosensitivity and can be used to model hypoxia-induced radioresistance, highlighting their potential as personalized tools for studying therapeutic response mechanisms in HNSCC.