Chapter 4 │ Page 140 Since MICA/B proteins are recognized as stress proteins, induced in tumor cells encountering DNA damage [66], we hypothesized augmentation of ligand expression profile in the di erent HNSCC cell lines one day post NTP exposure. Indeed, NTP treatment e ects mostly manifested in 24h, with an upregulation of MICA/B on the cellular membrane of all three cell lines compared to untreated controls. Once again, this trend was more pronounced for the higher treatment regimen. Interestingly, the SCC22B cell line, which exhibited the least expressional changes for the inhibitory ligand panel, was strongly positive for MICA/B expression with an 84% increase in ΔMFI compared to baseline (1 vs 1.84; p = 0.0297), as displayed in the right panel of Figure 8. 4. DISCUSSION In this study, we investigated the e ects of NTP on di erent tumorassociated immune checkpoint ligands for NK cells. We used computational methods to gain insight into the e ect of NTP-induced chemical changes on MHC Class I molecules HLA-Cw4 and HLA-E, and how the resulting conformational changes a ect biological properties like receptor-ligand binding a inity. Furthermore, we experimentally investigated the oxidation-induced e ects of NTP on these cell surface molecules, and broadened our scope to other key immune checkpoints a ecting NK cell functioning, providing valuable information for subsequent immunological studies. We distinguished between immediate oxidation e ects and downstream cellular responses in the cancer cells. Immediate modifications (0h analysis) to expression profiles were attributed to oxidation-induced e ects, as literature delineates this as the most proficient chemical modification [28, 31, 32, 67]. Besides these transient chemical alterations, the reactive species in NTP cause a cascade of downstream cellular reactions, including metabolic alterations, dysregulation of the anti-oxidant system, and changes in genetic and phenotypic expression profiles (24h analysis) [14, 56, 68, 69].
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