Figure 5.
ADU-S100 STING agonist inhibits pancreatic cancer growth and inflames distal untreated tumors. Mice were synchronously implanted with dual-flank KPC tumors and treated twice with 100 μg S100 (purple) or vehicle control (black) injected to a single-flank. Tumors were harvested for flow cytometric analysis 2 days after second treatment. (A) Injected and contralateral tumor volume at study end. (B) Tumor growth kinetics of injected (top) and contralateral (bottom) tumors. (C) Waterfall plot of percent change in tumor area from day 12, before first treatment, to endpoint; each bar represents an individual mouse. Dotted horizontal lines represent the mean of each group. (D) Cell frequencies and phenotypes were analyzed in contralateral tumors. Representative CD4+-by-CD8+ T cell contour plot. (E–G) Cellular composition of the injected (iTDLNs) and contralateral (cTDLNs) tumors and within the spleen. Ratio of CD4:CD8 cells in these lymphoid tissues (E). Phenotype of CD8+cells measured by CD62L, CD69, CD44, GzmB, IFNγ, and CXCR3 expression in TDLNs (F) and spleen (G). Error bars represent mean ± SEM (A, D, and E) or mean ± SD (B). n = 10 from 2 independent experiments (A–C), n = 5 (D and E). ns, not significant. ∗P < .05, ∗∗P < .01, ∗∗∗P < .001, ∗∗∗∗P < .0001. GzmB, granzyme B; MFI, median fluorescence intensity.