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Int. J. Mol. Sci. 2018, 19(10), 2885; https://doi.org/10.3390/ijms19102885

The Role of Stroma in Cholangiocarcinoma: The Intriguing Interplay between Fibroblastic Component, Immune Cell Subsets and Tumor Epithelium

1
Department of Experimental and Clinical Medicine, University of Florence, 50141 Florence, Italy
2
Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, 20089 Rozzano, Italy
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 28 August 2018 / Revised: 18 September 2018 / Accepted: 20 September 2018 / Published: 22 September 2018
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Abstract

Cholangiocarcinoma (CCA) is a severe and mostly intractable adenocarcinoma of biliary epithelial cells. A typical feature of CCA is its highly desmoplastic microenvironment containing fibrogenic connective tissue and an abundance of immune cells (T lymphocytes, Natural Killer (NK) cells, and macrophages) infiltrating tumor epithelium. This strong desmoplasia is orchestrated by various soluble factors and signals, suggesting a critical role in shaping a tumor growth-permissive microenvironment that is responsible for CCA poor clinical outcome. Indeed stroma not only provides an abundance of factors that facilitate CCA initiation, growth and progression, but also a prejudicial impact on therapeutic outcome. This review will give an overview of tumor-stroma signaling in a microenvironment critically regulating CCA development and progression. Identification of CCA secreted factors by both the fibroblast component and immune cell subsets might provide ample opportunities for pharmacological targeting of this type of cancer. View Full-Text
Keywords: cholangiocarcinoma; desmoplastic stroma; tumor microenvironment; tumor-associated macrophages; cancer associated fibroblasts cholangiocarcinoma; desmoplastic stroma; tumor microenvironment; tumor-associated macrophages; cancer associated fibroblasts
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Gentilini, A.; Pastore, M.; Marra, F.; Raggi, C. The Role of Stroma in Cholangiocarcinoma: The Intriguing Interplay between Fibroblastic Component, Immune Cell Subsets and Tumor Epithelium. Int. J. Mol. Sci. 2018, 19, 2885.

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