Figure 4.

Gene set enrichment analysis (GSEA) revealed significant up-regulation of TNF-a (via NFkβ) and down-regulation of IL2-STAT5 signaling in the peripheral T cells from AGI-101H-vaccinated patients with melanoma.

(a) All 19,285 genes were sorted based on their log2FC value between AGI-101H-immunized patients and untreated patients (c) resulting in a pre-ranked gene list that was further used in a GSEA analysis with Molecular Signature Database Hallmark Gene Set Collection as the gene set database. Only biological processes with a nominal p-value < 0.05 and FDR < 10% are presented. (b) Activation of TNF-α in the peripheral T lymphocytes of patients with melanoma 6 days following administration of AGI-101H confirms significant activation of the anti-tumor response and of T cell differentiation into functionally distinct lineages. (c) Down-regulation of IL2-STAT5 signaling in the peripheral T lymphocytes from patients with melanoma 6 days following AGI-101H immunization. (d) Heatmap presenting the expression of TNF-α (via NFkB) signaling hallmark genes (top) and TGF-β signaling hallmark genes (bottom) in the peripheral T cells from healthy subjects, untreated patients with melanoma, and AGI-101H-immunized patients (average expression for each group). Blue – the lowest value in each column, orange – the highest value in each column. (e) Heatmap presenting the expression of IL2-STAT5 signaling hallmark genes in the peripheral T cells from healthy subjects, untreated patients with melanoma, and AGI-101H-immunized patients (average expression for each group). Blue – the lowest value in each column, orange – the highest value in each column.