Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer with a 5-year survival rate below 10%. This tumor has a high therapy resistance, largely due to its dense desmoplastic stroma, formed by pancreatic stellate cells. Immunotherapy seeks to restore anti-tumor immunity, with cell-based approaches showing promise. However, PDAC's suppressive tumor microenvironment presents major challenges, requiring strategies to enhance immune cell function and accessibility. Non-thermal plasma (NTP) is an emerging anti-cancer therapy generating reactive oxygen and nitrogen species, inducing oxidative stress in malignant cells leading to apoptosis while sparing healthy tissue. Additionally, NTP demonstrates immunomodulatory properties, potentially enhancing anti-tumor immunity. Therefore, I hypothesize that combining NTP with cell-based immunotherapy offers a strategy to improve PDAC treatment outcomes. To test this hypothesis, I will first evaluate the sensitization effect of NTP towards cell-based immunotherapy using the 3D PDAC microtumor in vitro model. Subsequently, I will investigate the therapeutic efficacy of the combination therapy in this 3D microtumor model utilizing live-cell imaging. Finally, I will assess the immunomodulatory impact of the therapy in a syngeneic mouse model. Altogether, my project aims to establish a novel therapeutic strategy to overcome PDAC's resistance mechanisms, in order to reduce relapse rates and significantly improve patient outcome.
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