Cholangiocarcinoma cell proliferation is enhanced in primary sclerosing cholangitis: A role for IL‐17A

Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the biliary tree and a risk factor for development of cholangiocarcinoma (CCA). The pathogenesis of PSC‐related CCA is largely unclear, although it is assumed that chronic inflammatory environment plays a pivotal role. We aimed to investigate the effect of inflammation‐related cytokines in PSC on the proliferation rate of cancer cells. For this, the proliferation index in PSC‐CCA and sporadic CCA was determined by Ki‐67 immunohistochemistry. The percentage of Ki‐67 positivity in cancer cells was significantly higher in PSC‐CCA than in sporadic CCA (41.3% ± 5.7% vs 25.8% ± 4.1%; P = .038). To assess which cytokines in the inflammatory environment have the potential to stimulate cancer cell proliferation, patient‐derived CCA organoids (CCAOs) were exposed to five cytokines related to PSC (Interleukin (IL)‐1β, IL‐6, IL‐17A, interferon gamma and tumor necrosis factor alpha). Only IL‐17A showed a significant stimulatory effect on cell proliferation in CCAOs, increasing organoid size by 45.9% ± 16.4% (P