Format

Send to

Choose Destination
Liver Int. 2019 May;39 Suppl 1:63-78. doi: 10.1111/liv.14098.

The tumour microenvironment and immune milieu of cholangiocarcinoma.

Author information

1
Department of Molecular Medicine, University of Padua, Padova, Italy.
2
Liver Center and Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut.
3
Department of Liver and Gastrointestinal Diseases, Biodonostia Health Research Institute - Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastián, Spain.
4
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, Madrid, Spain.
5
IKERBASQUE, Basque Foundation for Science, Bilbao, Spain.
6
Department of Gastroenterology and Hepatology, University Hospital Zürich, Zürich, Switzerland.
7
Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
8
Department of General, Visceral and Transplantation Surgery, RWTH Aachen University Hospital, Aachen, Germany.
9
Department of Surgery, Maastricht University Medical Centre, Maastricht, The Netherlands.
10
ESCAM - European Surgery Center, Aachen and Maastricht, Germany and The Netherlands.
11
NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands.
12
Division of Internal Medicine and Hepatology, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy.
13
Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.
14
Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
15
Department of Visceral, Thoracic and Vascular Surgery, University Hospital, Technische Universität Dresden, Dresden, Germany.
16
Institute of Experimental Immunology, University Hospital, Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
17
Department of Hematology and Medical Oncology, University Hospital Zürich, Zürich, Switzerland.

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.

KEYWORDS:

cancer associated fibroblasts; extracellular matrix; immune cells; immunotherapy; tumor associated macrophages; tumor reactive stroma

PMID:
30907492
DOI:
10.1111/liv.14098

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center