The tumour microenvironment and immune milieu of cholangiocarcinoma

Luca Fabris*, Maria J. Perugorria, Joachim Mertens, Niklas K. Bjorkstrom, Thorsten Cramer, Ana Lleo, Antonio Solinas, Hanna Saenger, Veronika Lukacs-Kornek, Anja Moncsek, Alexander Siebenhuner, Mario Strazzabosco

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review

53 Citations (Web of Science)

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.

Original languageEnglish
Pages (from-to)63-78
Number of pages16
JournalLiver International
Volume39
DOIs
Publication statusPublished - May 2019

Keywords

  • cancer associated fibroblasts
  • immunotherapy
  • extracellular matrix
  • immune cells
  • tumor associated macrophages
  • tumor reactive stroma
  • EPITHELIAL-MESENCHYMAL TRANSITION
  • CANCER-ASSOCIATED FIBROBLASTS
  • NATURAL-KILLER-CELLS
  • CARCINOMA-ASSOCIATED FIBROBLASTS
  • NEUTROPHIL-TO-LYMPHOCYTE
  • HEPATIC STELLATE CELLS
  • INTRAHEPATIC CHOLANGIOCARCINOMA
  • INFILTRATING LYMPHOCYTES
  • PROGNOSTIC-SIGNIFICANCE
  • DENDRITIC CELLS

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