The tumour microenvironment and immune milieu of cholangiocarcinoma

Tumor 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. Tumor
microenvironment comprises not only stromal cells, mainly cancer-associated
fibroblasts, but also immune cells of both the innate and adaptive system
(tumor-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 remodeled extracellular matrix, where
the tumor 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 due to 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 tumor-promoting function of the tumor
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. This article is protected by copyright. All rights reserved.