Additional Documents │ Page 221 English Summary The immune system remains one of the strongest defense mechanisms against cancer and immune-engaging therapies have therefore become a cornerstone of modern cancer management. However, despite clear successes, treatments like immune checkpoint inhibition (ICI) still face significant limitations, especially in solid tumors with a hostile and immune-deprived tumor microenvironment (TME). While precision medicine aims to overcome these hurdles through personalized approaches, strategies with a broad application potential still have their value, especially when they can enhance tumor immunogenicity. During my PhD, I investigated the immunomodulatory capacity of non-thermal plasma (NTP) with the purpose to incorporate it as a potent adjuvant for current treatment options. The generated reactive oxygen and nitrogen species (ROS/RNS) in NTP are reported to induce oxidative stress and immunogenic cell death (ICD), and thus hold potential to enhance tumor immunogenicity and improve both innate and adaptive immune recruitment. Before assessing therapeutic e icacy, rigorous experimental considerations were necessary. In research chapter 2, I demonstrated that fluorophore-induced phototoxicity alters intracellular redox homeostasis and increases cancer cell sensitivity to NTP, raising awareness for a major confounding factor for redox-based therapy research. This work highlights the importance of methodological optimization in fluorescence-based imaging studies, especially in the growing field of complex 3D tumor models and live-cell tracking. Building on previous research establishing NTP as a bona fide ICD inducer, I investigated in my research chapter 3 whether NTP could enhance the immunogenicity of conventional cisplatin (cis-diamminedichloroplatinum (II), CDDP) administration, a standard treatment for head and neck cancer squamous
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