MINI REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Cancer-Associated Fibroblasts in Cholangiocarcinoma: The Central Nexus of Tumor-Stroma Crosstalk and Therapeutic Translation
Provisionally accepted
- 兰州大学, 兰州市, China
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Cholangiocarcinoma (CCA) is a highly invasive malignant tumor of the biliary tract, and its detection is commonly delayed until advanced stages owing to a lack of early symptoms,with dismal overall survival and a high propensity for chemoresistance. CCA is primarily classified based on its anatomical location,encompassing distinct molecular subtypes with both intertumoral and intratumoral heterogeneity. Beyond malignant epithelial cells, CCA harbors a complicated and dynamically evolving tumor microenvironment (TME), in which multiple stromal cell types orchestrate disease progression through intricate crosstalk networks. Among them, cancer-associated fibroblasts(CAFs) constitute the numerically predominant cellular component in the matrix of CCA, playing pivotal roles in extracellular matrix remodeling, immune regulation, angiogenesis, and metastasis. Traditionally regarded as predominantly tumor-promoting, CAFs have recently been recognized as a heterogeneous population with transcriptionally and functionally distinct subsets, some of which may even exert tumor-suppressive functions. Deciphering the complex biology of CAFs is crucial for advancing CCA therapy. This review provides a thorough examination of the origins, functions, and pro-tumorigenic mechanisms of CAFs in the CCA TME, alongside a critical evaluation of advancements and obstacles in the development of therapies targeting CAFs.
Keywords: Cholangiocarcinoma, cancer-associated fibroblasts, heterogeneity, interactions, targeted therapy
Received: 15 Oct 2025; Accepted: 25 Nov 2025.
Copyright: © 2025 Rui, Liu, Zhao, Zhu, Liao and Zhou. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Wence Zhou
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