The tumour microenvironment and immune milieu of cholangiocarcinoma
Open accessAbstract
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.
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Reduced T and B lymphocyte intrahepatic and increased tumor-associated intrahepatic and CD14+CD16+ circulating monocyte numbers are associated with poor survival in patients with intrahepatic cholangiocarcinoma.
“Reduced T and B lymphocyte intrahepatic and increased tumor-associated intrahepatic and CD14+CD16+ circulating monocyte numbers are associated with poor survival in patients with intrahepatic cholangiocarcinoma [214–217].”
From Inflammation and immunity in liver homeostasis and disease: a nexus of hepatocytes, nonparenchymal cells and immune cells (2025) · cites this paper as [214]
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Flagged first, then by citations
Research works printed but not linked: 2
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Cited by
Sorted by citations
Cholangiocarcinoma 2020: the next horizon in mechanisms and management
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Self-citationCholangiokines: undervalued modulators in the hepatic microenvironment
Cai, X., Tacke, F., Guillot, A., & Liu, H. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1192840 · Cited by 40 · see citing works
- Authors
- Fabris, L., Perugorria, M. J., Mertens, J., Björkström, N. K., Cramer, T., Lleo, A., Solinas, A., Sänger, H., Lukacs‐Kornek, V., Moncsek, A., Siebenhüner, A., & Strazzabosco, M.
- Affiliations
- University of Padua (IT)
- Department of Liver and Gastrointestinal Diseases Biodonostia Health Research Institute – Donostia University Hospital, University of the Basque Country (UPV/EHU) San Sebastián Spain
- University Hospital Zurich (CH)
- Karolinska University Hospital (SE)
- Maastricht University Medical Centre (NL)
- Division of Internal Medicine and Hepatology Humanitas Clinical and Research Center IRCCS Rozzano Italy
- University of Sassari (IT)
- Technische Universität Dresden (DE)
- University of Bonn (DE)
- Yale University (US)
- Corresponding author
- Fabris, Luca
- ORCID
- Venue
- Liver International
- Publisher
- Wiley
- Published
- 2019-05
- Volume
- 39
- Issue
- S1
- Pages
- 63-78
- ISSN
- 0106-9543 (ISSN-L)
- 1478-3223
- 1478-3231
- PMC
- PMC10878127
- OpenAlex
- W2942656542
- Cited by
- 187
- References
- 161
- Citations by year
- 2026: 13 · 2025: 12 · 2024: 28 · 2023: 41 · 2022: 42 · 2021: 22 · 2020: 24 · 2019: 4
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Liver International (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- PubMed Central (acceptedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, other-oa)
- UnissResearch (Università degli Studi di Sassari) (submittedVersion, other-oa)
- BOA (University of Milano-Bicocca) (submittedVersion)
- Padua Research Archive (University of Padova) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich)
- Funders
- National Institutes of Health (DK034989, RO1DK-079005-07, RO1DK096096)
- Fondazione Banco di Sardegna (2014-0188)
- PSC Partners Seeking a Cure
- Università degli Studi di Padova
- Connecticut Innovations (16-RMA-YALE-26)
- Topics
- Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
- Health Sciences › Medicine › Hepatology › Liver Diseases and Immunity
- Health Sciences › Medicine › Surgery › Pediatric Hepatobiliary Diseases and Treatments
- Keywords
- cholangiocarcinoma, intrahepatic cholangiocarcinoma, tumor microenvironment, desmoplasia, cancer-associated fibroblasts, tumour-associated macrophages, tumor-associated neutrophils, natural killer cells, T cells, B cells, extracellular matrix remodeling, cholangiocytes, tumor stroma, cancer immunotherapy
- MeSH terms
- Animals, Bile Duct Neoplasms, Disease Models, Animal, Fibroblasts, Humans, Immunity, Innate, Cholangiocarcinoma, Endothelial Cells, Adaptive Immunity, Tumor Microenvironment
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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