Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation

IF 9.1 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2026-08-21 DOI:10.1038/s41388-026-03961-z

Wenqi Xu, Shuhan Liu, Longlong Sun, Yao Bi, Zhenhua Lin, Tong Wang, Xiangshan Ren, Renbo An

{"title":"Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation","authors":"Wenqi Xu, Shuhan Liu, Longlong Sun, Yao Bi, Zhenhua Lin, Tong Wang, Xiangshan Ren, Renbo An","doi":"10.1038/s41388-026-03961-z","DOIUrl":null,"url":null,"abstract":"Cholangiocarcinoma (CCA) remains a therapeutic challenge due to its “immune cold” phenotype, defined by a desmoplastic fortress and profound T cell exclusion. This review characterizes the multi layered immune escape mechanisms, ranging from defective antigen presentation to the recruitment of suppressive myeloid cells and fibroblasts. We detail how physical barriers and the gut-liver axis conspire to maintain immune invisibility. Moving beyond mechanism, we critically evaluate emerging strategies designed to breach these defenses and reprogram the tumor microenvironment, including stromal targeting, mRNA vaccines, and combinatorial immunotherapies. We conclude by delineating the paradigm shift toward precision immuno oncology, highlighting that resolving spatiotemporal heterogeneity through multi-omics integration is essential for transforming CCA into an immune responsive state. Additionally, the synergy between AI and intelligent medicine provides a novel roadmap for advancing CCA clinical therapeutics.","PeriodicalId":19524,"journal":{"name":"Oncogene","volume":"45 39","pages":"4101-4116"},"PeriodicalIF":9.1000,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Oncogene","FirstCategoryId":"3","ListUrlMain":"https://www.nature.com/articles/s41388-026-03961-z","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Cholangiocarcinoma (CCA) remains a therapeutic challenge due to its “immune cold” phenotype, defined by a desmoplastic fortress and profound T cell exclusion. This review characterizes the multi layered immune escape mechanisms, ranging from defective antigen presentation to the recruitment of suppressive myeloid cells and fibroblasts. We detail how physical barriers and the gut-liver axis conspire to maintain immune invisibility. Moving beyond mechanism, we critically evaluate emerging strategies designed to breach these defenses and reprogram the tumor microenvironment, including stromal targeting, mRNA vaccines, and combinatorial immunotherapies. We conclude by delineating the paradigm shift toward precision immuno oncology, highlighting that resolving spatiotemporal heterogeneity through multi-omics integration is essential for transforming CCA into an immune responsive state. Additionally, the synergy between AI and intelligent medicine provides a novel roadmap for advancing CCA clinical therapeutics.

Abstract Image

查看原文本刊更多论文

胆管癌：揭示冷肿瘤微环境和免疫再生策略。

胆管癌（CCA）仍然是一个治疗挑战，由于其“免疫冷”表型，定义的结缔组织的堡垒和深度T细胞排斥。本文综述了多层免疫逃逸机制，从缺陷抗原呈递到抑制性骨髓细胞和成纤维细胞的募集。我们详细介绍了物理屏障和肠-肝轴如何共同维持免疫隐身。除了机制之外，我们批判性地评估了旨在破坏这些防御和重新编程肿瘤微环境的新兴策略，包括基质靶向，mRNA疫苗和组合免疫疗法。最后，我们描述了向精确免疫肿瘤学的范式转变，强调通过多组学整合解决时空异质性对于将CCA转化为免疫应答状态至关重要。此外，人工智能和智能医学之间的协同作用为推进CCA临床治疗提供了新的路线图。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.