Fig. 1.

TLC388 significantly increased the STING-dependent pathway by promoting ssDNA accumulation in CRC. (A) The association between TMEM173 (STING) signature and cancer immunogenicity-related gene signature were analyzed. The gene expression data were retrieved from TCGA-COAD (n = 254). (B) The association between TMEM173 (STING) and dendritic cells signatures were analyzed in TCGA-COAD cohort (n = 458) on TIMER2.0 website (http://timer.comp-genomics.org/timer/). (C) The representative images of tumor STING and tumor-infiltrating CD11c⁺ DCs in colorectal cancer patients (n = 259). (D) The relationship between tumor STING and infiltration of dendritic cells was examined in colorectal cancer patients (r = 0.103, n = 259, p < 0.001). (E) High tumor STING expression was associated with favorable CSS in colorectal cancer patients who received post-operative chemotherapy (n = 115, Log-rank p = 0.0411). (F) The representative images of tumor STING and tumor-infiltrating CD8 and CD4 signatures in TCGA-COAD cohort (n = 458) on TIMER2.0 website (http://timer.comp-genomics.org/timer/). (G) The total protein expression of STING in colorectal cancer cell lines. (H) HT29 and CT26 cells were treated with different topoisomerase I inhibitors topotecan (TPT, 0.5 µM), irinotecan (CPT11, 0.5 µM), and TLC388 (0.5 µM) for 24 h and analyzed by western blotting. (I) HT29 and CT26 cells were treated with TLC388 (0.5, 1 and 2.5 µM) for 24 h. The cytosolic fraction was isolated for single-stranded DNA analysis (n = 3). These data were obtained from three independent experiments, and the values represent the means ± S.D. One-Way ANOVA t-test