Chapter 4 │ Page 117 1. INTRODUCTION Immunotherapy has emerged as a groundbreaking approach in the fight against cancer, harnessing the body's own immune system to target and destroy cancer cells [1]. Despite their great potential, immunotherapies are not without challenges, which include treatment resistance, variable patient responses, and significant adverse e ects [2]. In this light, research continues to explore novel strategies to reinforce therapeutic e iciency while minimizing o -target e ects. The use of non-thermal plasma (NTP) in oncology has been the focus of intense research in recent years [3]. This partially ionized gas generates a complex mixture of reactive oxygen and nitrogen species (RONS) [4, 5]. Various RONS are involved in diverse biological processes, including functioning as messenger molecules [6]. In addition, these reactive species play a pivotal role in inflammation and immune cell functioning [7-9]. Indeed, beside the direct cytotoxic e ects on cancer cells, the focus in plasma-oncology research lies increasingly on the immunotherapeutic potential of NTP treatment [10, 11]. Recent studies have demonstrated that NTP can induce immunogenic cell death [11-14], a cell death mechanism that increases the visibility of the cancer cells to the immune system [15]. In addition, NTP treatment has shown positive e ects on various immune cell types: macrophages exhibited an improved response against plasma-treated cancer cells [16, 17], while dendritic cells indicated improved infiltration and antigen presentation after treatment in vivo [18]. On the other hand, the e ect of NTP on other immune cells, such as natural killer (NK) cells, has not yet received much attention [11]. NK cells are lymphocytes of the innate immune system that play a major role in the body’s cancer immunosurveillance [19]. Because of their ability to directly recognize and kill cancer cells, they form an attractive target in immunotherapy [20, 21]. We have previously reported that treatment of skin cancer cells with NTP augmented NK cell-mediated toxicity in vitro [22]. Improved NK cell cytotoxicity was also shown in
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