Fig. 5: Functional validation of novel drug targets.
a, Schematic showing the PDE experimental validation platform. All experiments used n = 8 melanoma PDEs, with dimethyl sulfoxide (DMSO) being used as the control condition. b, Effect of perturbing OSM–OSMR on dysfunctional (PD-1+TCF-7−CD39+) and pre-dysfunctional (PD-1+TCF-7+CD39−) CD8+ T cells. Points are coloured by sample. P values from a paired two-sided Wilcoxon signed-rank test are shown. Data represent n = 8 melanoma PDEs. The centre line indicates the median, box borders represent the upper and lower quartiles, and whiskers represent the interquartile range multiplied by 1.5. c, Changes observed in CD4+ and CD8+ functional markers following OSM–OSMR blockade. * indicates P < 0.05. Exact P value for the significant change observed in CD4+GZMB+ Teff: P = 0.0156, paired two-sided Wilcoxon signed-rank test. Data represent n = 8 melanoma PDEs. Numerical values annotated on the plot represent the median. On the radar plot, for visual clarity, the maximum annotated value = maximum value of that quantity + (maximum value of that quantity × 10%) and the minimum point = minimum value of that quantity – (minimum value of that quantity × 10%). The y axis represents the percentage of parental population (Supplementary Fig. 11 shows the gating strategy), with the maximum and minimum points defined as above. d, Inhibiting PTPN22 did not significantly alter dysfunctional (PD-1+TCF-7−CD39+) or pre-dysfunctional (PD-1+TCF-7+CD39−) CD8+ T cells. Points are coloured by sample. Data represent n = 8 melanoma PDEs. P values from a paired two-sided Wilcoxon signed-rank test are shown. The centre line indicates the median, box borders represent the upper and lower quartiles, and whiskers represent the interquartile range multiplied by 1.5. e, Changes in CD4+ and CD8+ T cell functional markers following the inhibition of PTPN22. Data were analysed using a paired two-sided Wilcoxon signed-rank test and no significant changes were observed. Data represent n = 8 melanoma PDEs. Numerical values annotated on the plot represent the median. On the radar plot, for visual clarity, the maximum annotated value = maximum value of that quantity + (maximum value of that quantity × 10%) and the minimum point = minimum value of that quantity – (minimum value of that quantity × 10%). The y axis represents the percentage of parental population (Supplementary Fig. 11 shows the gating strategy), with the maximum and minimum points defined as above. f, CCL4 expression level by cytokine bead array in n = 8 melanoma PDEs following anti-OSM treatment. P value, from a paired two-sided Wilcoxon signed-rank test, for the difference in CCL4 expression between anti-OSM and control = 0.0391. The centre line indicates the median, box borders represent the upper and lower quartiles, whiskers represent the interquartile range multiplied by 1.5, and black points are outliers. Illustration in a created in BioRender; Augustine, M. http://biorender.com/k5w99jf (2026).
