TNF and cholangiocarcinoma: And the CCL5/CCR5 axis promotes the metastasis and growth of CCA by Akt/NF‐κB signalling which enhances the expression of metal matrix proteinase (MMP).59 As an upstream activator of STAT3, IL‐6 induces malignant transformation and metastasis of CCA.60 In addition, TNF‐α can regulate EMT to accelerate CCA invasion.61 Taken together, interleukin, growth factors, chemokines, proangiogenic factors, and modifying enzymes secreted by CCA stromal cells establish a network of cytokines to impact CCA progression.