Abstract
Advanced stages of head and neck squamous cell carcinoma (HNSCC) often face relapse or metastasis, and a miserable prognosis. First-line immunotherapy, with/without chemotherapy, displays limited benefits due to low response rates and severe side effects in weakened patients, compounded by high costs. In response, I will investigate an innovative, well-tolerable, and cost-efficient combination strategy to enhance approved therapies for this hard-to-treat cancer. Non-thermal plasma (NTP) is a localized ionized gas therapy that has been shown to activate the immune system and to induce cell death via disrupting the redox balance. To date, clinical use of NTP does not have reported major side effects. In addition, a well-tolerated, repurposed drug, shown to modulate immunity and redox metabolism, will be explored for its potential synergy with NTP. Therefore, I hypothesize that this combination, by altering redox balance, will enhance the effectiveness of (immuno)therapies for HNSCC through increased oxidative stress, cell death, and anti-tumor immunity. I will use 3D in vitro cancer models, primary patient material, and in vivo mouse models to evaluate the tumor kinetics, immune engagement, and therapy effectiveness. Successful completion of my project will lead to a combination strategy of NTP with repurposing drugs to improve the efficacy of first-line HNSCC therapies, while supporting the patient's quality of life.
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