Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumors with dismal prognosis. During the last years, different studies have highlighted the key role of the immune system in the development of CCA. Although immune cells can carry out anti-tumor immune responses, they can also be influenced in the presence of the tumor to support tumor growth through different aspects, such as suppressing the activity of other immune cells in the tumor microenvironment (TME). Thus, targeting the immune system is a promising approach for anti-cancer therapy. The macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor found on particular subsets of macrophages that has been described to play a determining role in macrophage polarization and consequently in adaptive immune responses in many solid tumors. This study aims to unravel the role of MARCO in CCA development and progression.