Endocrine Abstracts

Head and neck cancer (HNC) represents one of the most diagnosed cancer types. To date, radiotherapy is among the main approaches for the HNC treatment. Radiation of tumors unavoidably results in off-side effects on the surrounding tissues, such as the thyroid, causing hypothyroidism. Previous studies have revealed that radiation can damage thyroid cells directly, impair their mitosis, or induce an auto-immune response. Here, we investigate thyroid stem-like cells’ faith following radiation damage by exploiting mouse-derived thyroid organoids. It was shown that irradiation-induced damage of single cells isolated from mice thyroid glands impairs their ability to grow organoids in a dose-dependent manner, compromising their stemness. Furthermore, irradiation of formed thyroid organoids increases cell death and decreases cell stemness, inducing an in vitro differentiation process, as observed by gene expression analysis. This also revealed that, following irradiation, several interferon-related genes mainly involved in the innate immune response to viral infections are activated, such as cytokines, chemokines, and pattern recognition receptors (PRRs). Sequencing data from irradiated thyroid organoids gave a hint about the dysregulated processes to deepen in order to unveil potential targets to exploit to prevent this side effect. The molecular events observed underline the radiation-dysregulated pathways, factors leading to tissue damage and misfunctioning, giving more information about the causes underlying hypothyroidism. Knowing the molecular mechanisms responsible for healthy tissue damage occurring with radiotherapy is fundamental to counteract them and prevent side effects, improving the patient’s post-cancer treatment quality of life.