Department of Experimental and Clinical Medicine, University of Florence, Florence 50141, Italy.
Center for Autoimmune Liver Diseases, Humanitas Clinical and Research Center, Rozzano 20089, Italy.
Int J Mol Sci. 2018 Sep 22;19(10):2885. doi: 10.3390/ijms19102885.
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.
胆管癌（CCA）是一种严重且大多难以治疗的胆管上皮细胞腺癌。CCA 的一个典型特征是其高度纤维母细胞性的微环境，其中包含纤维生成性结缔组织和大量浸润肿瘤上皮的免疫细胞（T 淋巴细胞、自然杀伤（NK）细胞和巨噬细胞）。这种强烈的纤维母细胞增生是由各种可溶性因子和信号协调的，这表明它在塑造有利于肿瘤生长的微环境中起着关键作用，而这种微环境是导致 CCA 临床预后不良的原因。事实上，基质不仅提供了大量促进 CCA 起始、生长和进展的因子，而且对治疗结果也有不利影响。这篇综述将概述微环境中肿瘤-基质信号对 CCA 发生和发展的调控作用。鉴定由成纤维细胞成分和免疫细胞亚群分泌的 CCA 因子，可能为这种类型的癌症的药物靶向治疗提供充分的机会。
