• IMMUNOTHERAPY
• CHOLANGIOCARCINOMA
• CHEMOKINES

Liver cancer represents a huge global burden as the third leading cause of cancer deaths. While hepatocellular carcinoma accounts for 80%–90% of primary liver cancer diagnoses, the incidence of intrahepatic cholangiocarcinoma (ICC) is increasing in most countries.1 Although the restoration of T cell functions by immune checkpoint inhibitors (ICIs) has achieved unprecedented clinical responses in various malignancies, the role for immunotherapy in ICC remains to be established.1 The heterogeneous ICI responsiveness is influenced by a range of tumour cell-intrinsic factors, tumour-stroma factors including the immunosuppressive tumour microenvironment (TME) and host-related influences such as gut microbiota.2 Despite our improved understanding of the pathophysiology and genetic drivers of ICC,1 this knowledge is yet to be translated into clinical practice. In particular, the desmoplastic ICC has a rich stroma of immunosuppressive myeloid cells, including tumour-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs), which mediate immune escape by impairing T cell activity and proliferation that may undermine response to ICI.3 A major challenge for ICC immunotherapy is therefore the need to turn cold, T cell-dysfunctional tumours into hot, …