Fig 2: CD56dim NK cell degranulation toward OC cell lines is boosted by TIGIT blockade and inhibited by DNAM-1 blockade. (a) Healthy donor CD56dim NK cells fold change for CD107a and IFN? after 4 h stimulation with SKOV-3 target cells, low dose rhIL-15, and TIGIT, DNAM-1 and/or CD96 blockade or matching isotype controls. Fold change in CD107a and IFN? expression on CD56dim cells following antibody treatment is calculated relatively to the condition with low dose rhIL-15 and 4 h SKOV-3 stimulation only. Cumulative data are shown as mean+SEM (n = 6) (b) IGROV-1 and OVCAR-3 stimulation for 4 h in the presence of TIGIT and/or DNAM-1 blockade or matching isotype controls. Fold change in CD107a and IFN? expression on CD56dim cells following antibody treatment is calculated relatively to the condition with low dose rhIL-15 and 4 h IGROV-1 or OVCAR-3 stimulation only -3 (n = 6 for IGROV-1 and n = 6 for OVCAR). A One-Way repeated measure ANOVA with Bonferroni correction was used for statistical analysis, * p < .05, ** p < .01 and *** p < .001

Fig 3: DNAM-1, TIGIT and CD96 are dose-dependently upregulated by rhIL-15 and DNAM-1 is downregulated by OC tumor cells. (a) DNAM-1 (n = 8), TIGIT (n = 6) and CD96 (n = 5) expression on NK cells of healthy donors co-cultured with SKOV-3, IGROV-1 or OVCAR-3 spheroids and increasing rhIL-15 concentrations for 7 days. Data is shown as mean+SEM. One-Way ANOVA with Bonferroni correction was used for statistical analysis, * p < .05, ** p < .01 and *** p < .001. (b) DNAM-1, TIGIT and CD96 expression on healthy donor NK cells co-cultured with a patient-derived primary tumor cell line and increasing rhIL-15 concentrations for 7 days cultured in duplicate. (c) DNAM-1, TIGIT and CD96 expression on healthy donor NK cells co-cultured with patient-derived tumor cells and increasing rhIL-15 concentrations for 7 days cultured in duplicate