IL-6 was reported to induce the chemoresistance in cancer via activation of STAT3.43 IL-8 and VEGF were reported to activate STAT3 in cancer cells.44,45 The activation of STAT3 seems to be important for chemoresistance in cholangiocarcinoma cells.46 Moreover, activated STAT3 was reported to induce resistance to gemcitabine in pancreatic cancer.47,48 In this study, we showed that nintedanib not only suppressed the secretion of the cancer-promoting cytokines induced by CAFs, but also the phosphorylation of STAT3 in ICC cells, which is induced by CAFs. This evidence concerns the gene IL6 and cholangiocarcinoma.