Fig. 4

PI3Kα/δ promotes durable responses and improves T-cell memory and CD8 T-cell effector function in vivo. a Spider plot depicting durability of response in CT-26 bearing mice treated with AZD8835 50 mg/Kg twice daily for 4 intermittent cycles. Scatter plots showing frequencies of (b) CD4⁺ and (c) CD8⁺ splenic central memory (CM) cells relative to total CD45⁺ cells. d Scatter plot indicating increase in CD8+ T-cell frequencies in CT-26 tumors e Representative flow cytometry contour plots of tumor cytotoxic T activation/proliferation cell markers GzmB⁺/CD25⁺/Ki67⁺ and (f) Scatter plot shows quantification of GzmB⁺/CD25⁺/Ki67⁺ cytotoxic CD8⁺ T-cells. (g) PD-1 protein expression in CD8+ T-cells. h Scatter bar chart shows the concentration of interferon-γ in tumor aqueous extracts, as measured by LegendPLEX analysis. Gene expression data generated from a panel of 96 genes was used to calculate a GSVA score [32] indicating enrichment for specific immune cell types at each timepoint in (i) CT-26 and (j) MC-38 tumors 14 days after implant and 2 cycles of AZD8835 treatment. Error bars represent mean ± SEM, statistical differences were calculated using a 1-way ANOVA with post hoc analysis. Data are representative of 2 independent experiments. Statistical significance is indicated as follows: * p ≤ 0.05, ** p ≤ 0.01, *** p ≤ 0.001, **** p ≤ 0.0001