REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1651769
This article is part of the Research TopicImmuno-metabolic Approaches for the Treatment of Hepatobiliary and Pancreatic TumorsView all 5 articles
Immunotherapy in Biliary Tract Cancer: Reshaping the Tumour Microenvironment and Advancing Precision Combination Strategies
Provisionally accepted
- 1People's Hospital of Anshun city, guizhou, China
- 2Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, beijing, China
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Biliary tract cancer, which includes intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, and gallbladder cancer, presents a significant clinical challenge because of its aggressive nature and limited therapeutic options. Although standard chemotherapy regimens, such as gemcitabine and cisplatin, are used, the prognosis for advanced biliary tract cancer patients remains poor due to the rapid development of re-sistance. Recently, advancements in immunotherapy, particularly immune checkpoint inhibitors, have shown promise. However, the response rate in patients with biliary tract cancer is still suboptimal primarily because of the highly immunosuppressive tumour microenvironment. This microenvironment includes a complex network of tumour-associated macrophages, regulatory T cells, and myeloid-derived suppressor cells, all of which contribute to immune evasion. In this review, we discuss the molecular mechanisms that drive biliary tract cancer, focusing on genetic alterations and the role of the TME in immune suppression. We also examine current combination strategies that integrate immune checkpoint inhibitors with chemo-therapy and targeted therapies, which have demonstrated superior efficacy over monotherapy. Furthermore, we explore emerging therapeutic approaches, such as metabolic modulation, CAR-T-cell therapy, and mRNA vaccines, which are reshaping the treatment landscape. Finally, we highlight the need for personal-ized treatment strategies and the development of predictive biomarkers to guide therapy selection. Future research should focus on refining these combination therapies, optimizing patient selection, and validating biomarkers to improve clinical outcomes and survival in biliary tract cancer patients.
Keywords: Biliary tract cancer, Molecular mechanisms, Immunotherapy, Tumor Microenvironment, combination therapy precision treatment strategies
Received: 22 Jun 2025; Accepted: 21 Jul 2025.
Copyright: © 2025 Xue, Zhang, Zhang, Zhou and Zhao. 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, People's Hospital of Anshun city, guizhou, China
Haitao Zhao, Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, beijing, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.