Nguyen MLT, Bui KC, Scholta T, et al. - In this study, the role of IL‐6 signaling in cholangiocarcinoma carcinogenesis and efficacy of siltuximab treatment on cholangiocarcinoma in vitro and in vivo were explored. Applying reverse transcription real‐time polymerase chain reaction and immunohistochemistry, researchers examined the expression of IL‐6 on human cholangiocarcinoma cell lines and murine and human cholangiocarcinoma tissues. They tested the impact of an anti‐IL‐6 chimeric monoclonal antibody, siltuximab, in vitro by proliferation, migration, and two‐dimensional and three‐dimensional invasion assays and in vivo by a xenograft mouse model. This study’s findings demonstrate that interleukin 6 plays an essential role in cholangiocarcinoma carcinogenesis, and siltuximab has the potential to be considered as a new treatment option for cholangiocarcinoma patients. The expression of IL‐6 in human cholangiocarcinoma cells is high and, in the cholangiocarcinoma engineered mouse model, IL‐6 level is associated with tumor volume. Both in vitro and in vivo, siltuximab sufficiently inhibits IL‐6 signaling and progression of cholangiocarcinoma.