2. Academic Validation
  3. Radiation-induced interferon-I response impairs thyroid organoid function

Radiation-induced interferon-I response impairs thyroid organoid function

  • Radiother Oncol. 2026 Feb 21:218:111453. doi: 10.1016/j.radonc.2026.111453.
Rufina Maturi 1,  Davide Cinat 2,  Anne L Jellema-de Bruin 2,  Gabriella De Vita 3,  Schelto Kruijff 4,  Rob P Coppes 5,  Abel Soto-Gamez 6
Affiliations

Affiliations

  • 1 Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy; Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands.
  • 2 Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands.
  • 3 Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
  • 4 Department of Surgery, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands; Department of Nuclear Medicine and Molecular Imaging, University of Groningen. University Medical Center Groningen, Groningen, the Netherlands; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
  • 5 Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands. Electronic address: [email protected].
  • 6 Department of Biomedical Sciences, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands; Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Groningen 9713 GZ, the Netherlands. Electronic address: [email protected].
PMID: 41730478 DOI: 10.1016/j.radonc.2026.111453
Abstract

Background and aim: Radiotherapy is a standard Cancer treatment, but radiation exposure to surrounding healthy tissues may lead to adverse side effects that compromise patient quality of life. In patients with head and neck Cancer treated with radiotherapy, thyroid damage is a frequent complication, resulting in hypothyroidism or secondary thyroid malignancies. Although clinically recognized, the molecular mechanisms underlying these side effects remain mostly unexplored. This study aims to characterize the radiation-induced molecular alterations in thyroid organoids.

Methods: Bulk RNA Sequencing was performed to investigate transcriptomic changes in tissue-derived thyroid organoids following gamma-irradiation. Observed changes were further validated and explored using qPCRs, western blotting, immunofluorescence, Caspase 3/7 activity and Organoid forming efficiency.

Results: Our findings identify interferon-β signaling as a key mediator of radiation-induced inflammation in the thyroid. Additionally, the intrinsic apoptotic pathway was found to be the predominant mechanism of radiation-induced thyroid cell death. Notably, while IFN-β exhibited a protective effect against Apoptosis, it concurrently reduced thyroid stem progenitor cell potential.

Conclusions: These results highlight the dual role of interferon-β signaling in modulating thyroid cell fate after irradiation, potentially promoting survival upon injury at the expense of regenerative potential.

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