REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
This article is part of the Research TopicCommunity Series in Tumor Microenvironment and Metabolic Reprogramming in Cancer: Volume IIView all 12 articles
Metabolic Collusion Driving Immune Evasion in Cholangiocarcinoma: Un-masking the Dual Control of the Immuno-Metabolic Microenvironment
Provisionally accepted
- 1Anshun City People's Hospital, Anshun, China
- 2Peking Union Medical College Hospital, Beijing, China
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Cholangiocarcinoma represents an aggressive malignancy with poor prognosis, particularly for intrahepatic Cholangiocarcinoma. Despite recent advancements in chemotherapy and immune checkpoint blockade therapies, survival outcomes remain suboptimal. A key obstacle in treating Cholangiocarcinoma is its immune exclusion and resistance to Cholangiocarcinoma, which is influenced by metabolic reprogramming within the tumor microenvironment. This review explores the dual control of metabolism and immunity in Cholangiocarcinoma, highlighting the intricate interplay between metabolic pathways (e.g., glycolysis, lactate accumulation, fatty acid oxidation) and immune evasion mechanisms. We examine how bile acid signaling, hypoxia, and stromal interactions shape Cholangiocarcinoma's immune landscape, facilitating tumor progression and immune resistance. Moreover, we discuss emerging therapeutic strategies that target metabolic vulnerabilities to "convert" immune-excluded Cholangiocarcinoma into a more immunologically responsive state. These strategies include metabolic inhibitors targeting lactate, amino acid catabolism, and fatty acid metabolism, as well as approaches to modulate bile acid signaling. We propose that combining metabolic reprogramming with immune checkpoint blockade therapies holds significant promise in enhancing immune responses and improving therapeutic outcomes for Cholangiocarcinoma patients. This review provides a comprehensive framework for future research and clinical trials, aiming to bridge the gap between metabolic insights and immunotherapy in Cholangiocarcinoma treatment.
Keywords: Cholangiocarcinoma, Immune Evasion, metabolic reprogramming, Tumor Microenvironment, Bile acids, Combination immunotherapy
Received: 01 Sep 2025; Accepted: 14 Nov 2025.
Copyright: © 2025 Xue, Zhang, Zhang, Wu, Zhou and Lu. 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:
Kai Zhou, 396843122@qq.com
Xin Lu, luxin@pumch.cn
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