Chapter 6 │ Page 205 patters (DAMPs), dendritic cell (DC) activation and maturation in co-culture experiments, and in vivo validation of immune engagement [13, 14, 17-20]. In the second part of my study (Chapter 3), I aimed to take the next step and evaluate the robustness and consistency of ICD induction by NTP, in combination with conventional therapies, in this case the widely used chemotherapy cisplatin (cisdiamminedichloroplatinum (II), CDDP). For the past decades, platinum-based agent CDDP, an intercalating drug causing DNA damage, has been the backbone of most treatment regimens [21, 22]. It has long been thought that CDDP is non-immunogenic, but recent studies have shown its ability to induce some features of anti-tumor immunity under certain conditions [2326]. Furthermore, ICD induction can be improved when CDDP is combined with endoplasmic reticulum stressors/ICD inducers [25, 27]. Hence, I hypothesized that NTP could improve CDDP outcome via enhancing immunogenicity of tumor cell killing and stimulating the activation of subsequent anti-cancer immune responses. My findings demonstrated synergistic cytotoxic e ects of the NTP-CDDP combination on tumor kinetics. In addition to the cancer cell killing capacity, the combination therapy was able to induce a diverse spectrum of DAMPs and immune modulating signaling molecules, supporting the notion that NTP retained its immunogenic potential in a combinatorial setting. Most apparently, the NTP-CDDP combination significantly improved survival and reached almost 40% protection in an in vivo model for HNSCC, a benefit that was also observed with NTP monotherapy, but to a lower degree, and was absent in CDDP monotherapies. Strikingly, despite that this research approach is a means to introduce NTP as an immunomodulatory adjuvant in the clinic, relatively few studies have explored relevant combinations with standard-of-care therapies, exposing a critical gap in the field. Nevertheless, the reports that are available do indicate that NTP holds promise
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