Chapter 1 │ Page 20 1.6. Non-Thermal Plasma as Novel Strategy for ICD Induction and Immune modulation NTP has been reported to also have immunomodulatory properties, and our lab was the first to identify short-lived reactive species in plasma as major inducers of ICD [62]. In addition, several studies have touched the topic of ICD and immunomodulation via NTP exposure. Illustrative for that, in osteosarcoma, injectable plasma-treated alginate hydrogels triggered ICD hallmarks [68]. In melanoma, enhanced NK cell activity could be demonstrated both in vitro [91] and in vivo [64]. Additionally, in a colorectal cancer model, NTP demonstrated both immune protection in a vaccination setting, and tumor-specific T cell immune activation after the treatment of established tumors in vivo[92]. However, this field needs to be explored more to elucidate its full immunogenic potential. First, it is essential to determine whether NTP's ability to induce ICD remains e ective when combined with less immunogenic standard treatments. Only by demonstrating its robustness and compatibility with existing therapies, NTP will realize its full clinical potential. Given that current standard treatments are wellestablished and relatively successful, I see the clinical potential of NTP in a (neo) adjuvant approach rather than as a replacement of current therapies. Other areas of interest include a more profound understanding of how NTP modulates immune checkpoints and receptors, a promising gateway, as demonstrated previously in our studies on CD47 and CD44 [93, 94]. Moreover, its impact on innate immunity, particularly in activating NK cells, is a crucial factor that needs to be incorporated more broadly to understand NTP’s global immunological profile, rather than focusing solely on adaptive immune responses. Further investigation into these aspects will help position NTP as a complementary adjuvant in cancer treatment, particularly in the context of immune-engaging therapies, establishing its clinical relevance and expanding its potential in cancer immunotherapy.
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