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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.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1725948","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T06:29:25Z","timestamp":1765261765000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Cancer-associated fibroblasts in cholangiocarcinoma: the central nexus of tumor-stroma crosstalk and therapeutic 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