215P Differential spatial gene expression and clinicopathologic characteristics are associated with exceptional response to immune checkpoint inhibition in recurrent/metastatic head and neck cancer

NES3.57; p<0.0001) enrichment in BR patients derived NK cells in comparison to NR patients.In addition, NK cells from BR patients showed enrichment in oxidative phosphorylation genes (NES2.14;p<0.0001) as well as DNA repair pathway (NES2.07;p<0.0001).ISMARA analysis revealed that BR patients-derived NK cells showed high Interferon regulatory factor 3 (IRF3)-binding motif (Pearson corr.coeff. 0.76; p<0.0001) compared to the NR cohort.In vitro treatment of NK cells with DNA-PKi significantly increased multiple innate immunity cytosolic DNA/RNA sensors, namely cGAS-STING (p < 0.0001), MAVS (p < 0.0001) and IFI16 (p < 0.0001).Finally, metabolic analysis showed an increase in ATP production Rate and phenotypic characterization by flow cytometry showed an increase in ICOS (CD278) expression in DNA-PKi-treated NK cells.Conclusions: Comprehensive transcriptomic analysis of SCLC-isolated NK cells revealed significant positive modulation of innate immune pathways, suggesting a potential role for DNA-PKi in metabolic and phenotypic remodelling.