The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine.

The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine.

Publication date: Mar 09, 2019

Cholangiocarcinoma (CCA) is a deadly cancer of the biliary epithelium with limited therapeutic options. It is a heterogeneous group of cancer that could develop at any level from the biliary tree and is currently classified into intrahepatic, perihilar and distal based on its anatomical location. With incidence and mortality rates currently increasing, it is now the second most common type of primary liver cancer and represents up to 3% of all gastrointestinal malignancies. High-throughput genomics and epigenomics have greatly increased our understanding of CCA underlying biology, however its pathogenesis remains largely unknown. CCA is characterized by a highly desmoplastic microenvironment containing stromal cells, mainly cancer-associated fibroblasts, infiltrating tumor epithelium. Tumor microenvironment in CCA is a highly dynamic environment that, besides stromal and endothelial cells, encompass also an abundance of immune cells, of both the innate and adaptive immune system (including tumor-associated macrophages, neutrophils, natural killer cells, and T and B lymphocytes) and abundant proliferative factors. It is orchestrated by multiple soluble factors and signals, that eventually define a tumor growth-permissive microenvironment. Through complicate interactions with CCA cells, tumor microenvironment profoundly affects the proliferative and invasive abilities of epithelial cancer cells and plays an important role in accelerating neovascularization and preventing apoptosis of neoplastic cells. In this review, we discuss recent developments regarding the characteristics of the tumor microenvironment, the role of each cellular population, and their multiarticulate interaction with the malignant population. Further we discuss innovative treatment approaches, including immunotherapy, and how identification of CCA secreted factors by both the stromal component and immune cell subsets are leading towards a precision medicine in CCA.

Rimassa, L., Personeni, N., Aghemo, A., and Lleo, A. The immune milieu of cholangiocarcinoma: From molecular pathogenesis to precision medicine. 04214. 2019 J Autoimmun.

Concepts Keywords
Adaptive Immune System Epigenomics
Apoptosis Apoptosis
Biliary Tree Bile duct
Cancer Stromal cell
Cholangiocarcinoma Tumor microenvironment
Distal RTT
Endothelial Cells Connective tissue cells
Epigenomics Cholangiocarcinoma
Epithelial Tumor
Epithelium Oncology
Fibroblasts Hepatology
Gastrointestinal Clinical medicine
Immune Cells Medical specialties
Immunotherapy Medicine
Incidence Immunotherapy
Liver Cells cancer
Lymphocytes Tumor epithelium Tumor
Macrophages Immunotherapy Precision Tumor
Malignancies Developments characteristics tumor
Natural Killer Cells
Precision Medicine


Type Source Name
disease DOID Biliary tract cancer
disease MESH Biliary tract cancer
pathway BSID Apoptosis
disease MESH growth
disease MESH multiple
pathway BSID Adaptive Immune System
disease DOID primary liver cancer
disease DOID cancer
disease MESH cancer
disease DOID cholangiocarcinoma
disease MESH cholangiocarcinoma

Original Article

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