Fig. 4: ISM5939 protects tumor-secreted cGAMP and orchestrates non-cell autonomous STING activation in APCs.

A Dose-dependent accumulation of extracellular cGAMP by ISM5939. Cancer cell lines as indicated were treated with a gradient of ISM5939 concentrations followed by detection of supernatant cGAMP levels via ELISA (n = 2 biological replicates, two independent experiments). The color represents cGAMP concentrations. B, C Type I interferon (IFN) pathway activation in THP1-Dual cells co-cultured with (B) MDA-MB-231 (B) or (C) ZR-75-30 tumor cells transfected with dsDNA (n = 2 biological replicates, two independent experiments). D, E Type I IFN pathway activation in IRF3-deficient THP1-dual cells co-cultured with (D) MDA-MB-231 or (E) ZR-75-30 tumor cells transfected with dsDNA (n = 2 biological replicates, two independent experiments). F, G 4T1 syngeneic tumor-bearing mice treated with a single dose of ISM5939 (10 mg/kg, p.o.), and plasma and tumor samples assayed for (F) drug concentrations of ISM5939 and (G) cGAMP (orange) and IFNβ (green) in tumor tissues (n = 3 biological replicates). H Quantification of tumor infiltrating immune cells by flow cytometry in 4T1 syngeneic tumor bearing mice treated with ISM5939 (n = 6 biological replicates). Data were analyzed by two‐tailed Student’s t‐test. P-value < 0.05 were shown. All data were represented as mean ± SEM. Source data are provided as a Source Data file.