Immune Checkpoint Inhibitors: The Emerging Cornerstone in Cholangiocarcinoma Therapy?

Cholangiocarcinoma (CCA) is a term used to describe a category of biliary malignant tumors that have a poor prognosis. Different cells inside the peribiliary glands, such as hepatic stem/progenitors cells, cholangiocytes, hepatocytes, and/or multipotent stem cells, are vulnerable to neoplastic transformation, which helps to explain the great variety of these tumors. CCAs are characterized as Intrahepatic Cholangiocarcinoma (iCCA), Perihilar Cholangiocarcinoma (pCCA), and Distal Cholangiocarcinoma (dCCA) based on where they grow anatomically (dCCA). CCA is the second most prevalent primary liver neoplasm after Hepatocellular Carcinoma (HCC), accounting for 15% and 3% of all primary hepatic malignancies and gastrointestinal cancers, respectively, over the past few decades. Because the aetiology of CCA is largely unknown, it's possible that rising incidence patterns are due to new and yet-to-be-identified etiological causes. In this regard, several conditions have been identified as increasing the risk of cholangio carcinogenesis, including primary sclerosing cholangitis, cirrhosis, viral and parasitic infections, type 2 diabetes mellitus, and genetic landscape, while the role of others, such as non-alcoholic fatty liver disease and alcohol/tobacco consumption, is still debated. Furthermore, the lacks of symptomatology in the early stages of the disease, as well as the lack of specific screening tools, make it difficult to diagnose CCA early. As a result, most patients are discovered at an advanced stage when the cancer has already spread, reducing the efficacy of curative therapeutic options and ultimately leading to a poor prognosis and short life expectancy.