Year: 2019
Type: review
Abstract: 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.
Source: Liver International
DOI: 10.1111/liv.14098
Institutions: University of Padua, Yale University, Ikerbasque, University of the Basque Country, Instituto de Salud Carlos III, Biogipuzkoa Health Research Institute, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Donostiako Unibertsitate Ospitalea, University Hospital Zurich, Karolinska University Hospital, Karolinska Institutet, Maastricht University Medical Centre, Erasmus MC, Maastricht University, Universitätsklinikum Aachen, RWTH Aachen University, Humanitas University, IRCCS Humanitas Research Hospital, University of Sassari, Technische Universität Dresden, University of Bonn, University Hospital Bonn
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Connecticut Innovations, Yale University, Fondazione Banco di Sardegna, PSC Partners Seeking a Cure, Deutsche Forschungsgemeinschaft, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, Ministerio de Economía y Competitividad, Università degli Studi di Padova, Novo Nordisk Fonden, National Institutes of Health, European Regional Development Fund, Institute of Chemistry, Chinese Academy of Sciences, National Institute of Diabetes and Digestive and Kidney Diseases
Awards: G2082905234, G2923556567, G387698295, Cross talk between epithelial, inflammatory and mesenchymal cells in the development of portal fibrosis, G4555218899, Epithelial Angiogenic Signaling in Biliary Pathophysiology and in Polycystic Dise, CFTR modulates innate immune response in biliary epithelium: Role in the pathogenesis and treatment of Cystic-Fibrosis-related liver disease., Yale Liver Center
OpenAlex ID: W2942656542