The tumour microenvironment and immune milieu of cholangiocarcinoma

• Published in: Liver international Vol. 39; no. S1; pp. 63 - 78
• Main Authors: Fabris, Luca, Perugorria, María J., Mertens, Joachim, Björkström, Niklas K., Cramer, Thorsten, Lleo, Ana, Solinas, Antonio, Sänger, Hanna, Lukacs‐Kornek, Veronika, Moncsek, Anja, Siebenhüner, Alexander, Strazzabosco, Mario
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2019
• Subjects: Adaptive Immunity; Adaptive systems; Animals; Beta cells; Bile Duct Neoplasms - immunology; Bile Duct Neoplasms - physiopathology; Cancer; cancer associated fibroblasts; Cholangiocarcinoma; Cholangiocarcinoma - immunology; Cholangiocarcinoma - physiopathology; Disease Models, Animal; Endothelial cells; Endothelial Cells - immunology; Extracellular matrix; Fibroblasts; Fibroblasts - immunology; Fibroblasts - pathology; Humans; immune cells; Immune system; Immunity, Innate; immunotherapy; Invasiveness; Leukocytes (neutrophilic); Lymphocytes; Lymphocytes T; Macrophages; Medicin och hälsovetenskap; Natural killer cells; Pancreatic cancer; Stromal cells; tumor associated macrophages; Tumor Microenvironment - immunology; tumor reactive stroma; Tumors; tumor reactive stroma; tumor associated macrophages; immune cells; cancer associated fibroblasts; extracellular matrix; immunotherapy
• ISSN: 1478-3223; 1478-3231; 1478-3231
• DOI: 10.1111/liv.14098

Tumour microenvironment is a complex, multicellular functional compartment that, particularly when assembled as an abundant desmoplastic reaction, may profoundly affect the proliferative and invasive abilities of epithelial cancer cells. Tumour microenvironment comprises not only stromal cells, mainly cancer‐associated fibroblasts, but also immune cells of both the innate and adaptive system (tumour‐associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes), and endothelial cells. This results in an intricate web of mutual communications regulated by an extensively remodelled extracellular matrix, where the tumour cells are centrally engaged. In this regard, cholangiocarcinoma, in particular the intrahepatic variant, has become the focus of mounting interest in the last years, largely because of the lack of effective therapies despite its rising incidence and high mortality rates worldwide. On the other hand, recent studies in pancreatic cancer, which similarly to cholangiocarcinoma, is highly desmoplastic, have argued against a tumour‐promoting function of the tumour microenvironment. In this review, we will discuss recent developments concerning the role of each cellular population and their multifaceted interplay with the malignant biliary epithelial counterpart. We ultimately hope to provide the working knowledge on how their manipulation may lead to a therapeutic gain in cholangiocarcinoma.