Fig. 6

LY3300054 enhances peripheral T cell engraftment and activation and induces T cell inflamed phenotype in tumor tissues of CD34+ hHSC-engrafted NOG and NSG mice. Panels a, b, c, d: Blood from OV79-bearing CD34+ hHSC-engrafted NOG mice was analyzed for human T cell engraftment and phenotype using TruCount tubes on day 18 (pre-dose), day 34 (after three antibody doses), and day 46 (after four antibody doses). Peripheral T cell engraftment (A); CD8:CD4 ratio (B); PD-1 expression in CD4+ (C) and CD8+ T cells (D) cells. Results are represented as a geometric mean of engraftment + SEM with n = 9 mice on day 18 and day 34, and n = 5 mice on day 46. Two-way repeated measurements ANOVA was used for statistical analysis. Panel e: Gene expression analysis of tumor sample was performed using QuantiGene Plex assay. Volcano plots show Log2 fold-change of gene expression in the LY3300054 treated group compared to control group. The highlighted circles correspond to differentially expressed genes that display fold change > 1.7 (black solid vertical line) and p value < 0.05 (horizontal dotted line). Circle sizes are proportional to the level of expression in LY3300054 group. One-way ANOVA was used for statistical analysis. Panel f: Venn diagram showing the number of shared and tissue-specific DEGs (LY3300054 vs human IgG treatment) across various tissue types. Table on the right lists shared DEGsacross various tissues with fold-change > 1.7, p value < 0.05 for LY3300054 vs control