Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints

Yunyan Dai; Chenyang Dong; Zhiming Wang; Yunpeng Zhou; Yi Wang; Yi Hao; Pinggui Chen; Chaojie Liang; Gaopeng Li

doi:10.3389/fimmu.2024.1482291

Infiltrating T lymphocytes and tumor microenvironment within cholangiocarcinoma: immune heterogeneity, intercellular communication, immune checkpoints

Front Immunol. 2025 Jan 8:15:1482291. doi: 10.3389/fimmu.2024.1482291. eCollection 2024.

Authors

Yunyan Dai^#¹, Chenyang Dong^#², Zhiming Wang¹, Yunpeng Zhou¹, Yi Wang¹, Yi Hao¹, Pinggui Chen³, Chaojie Liang^{2

4}, Gaopeng Li^{1

5}

Affiliations

¹ Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
² First Clinical Medical College, Shanxi Medical University, Taiyuan, China.
³ Department of Nuclear Medicine, Nanyang First People's Hospital, Nanyang, Henan, China.
⁴ Department of biliary and Pancreatic Surgery, First Hospital of Shanxi Medical University, Taiyuan, China.
⁵ Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital, Taiyuan, China.

^# Contributed equally.

Abstract

Cholangiocarcinoma is the second most common primary liver cancer, and its global incidence has increased in recent years. Radical surgical resection and systemic chemotherapy have traditionally been the standard treatment options. However, the complexity of cholangiocarcinoma subtypes often presents a challenge for early diagnosis. Additionally, high recurrence rates following radical treatment and resistance to late-stage chemotherapy limit the benefits for patients. Immunotherapy has emerged as an effective strategy for treating various types of cancer, and has shown efficacy when combined with chemotherapy for cholangiocarcinoma. Current immunotherapies targeting cholangiocarcinoma have predominantly focused on T lymphocytes within the tumor microenvironment, and new immunotherapies have yielded unsatisfactory results in clinical trials. Therefore, it is essential to achieve a comprehensive understanding of the unique tumor microenvironment of cholangiocarcinoma and the pivotal role of T lymphocytes within it. In this review, we describe the heterogeneous immune landscape and intercellular communication in cholangiocarcinoma and summarize the specific distribution of T lymphocytes. Finally, we review potential immune checkpoints in cholangiocarcinoma.

Keywords: cholangiocarcinoma; immune checkpoints; immunotherapy; tumor microenvironment; tumor-infiltrating T lymphocytes.

Publication types

Review

MeSH terms

Animals
Bile Duct Neoplasms* / immunology
Bile Duct Neoplasms* / pathology
Bile Duct Neoplasms* / therapy
Cell Communication / immunology
Cholangiocarcinoma* / immunology
Cholangiocarcinoma* / pathology
Cholangiocarcinoma* / therapy
Humans
Immune Checkpoint Inhibitors / therapeutic use
Immune Checkpoint Proteins / genetics
Immune Checkpoint Proteins / metabolism
Immunotherapy / methods
Lymphocytes, Tumor-Infiltrating* / immunology
Lymphocytes, Tumor-Infiltrating* / metabolism
T-Lymphocytes / immunology
Tumor Microenvironment* / immunology

Substances

Immune Checkpoint Inhibitors
Immune Checkpoint Proteins

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by several funding sources: Shanxi Scholarship Council of China (Grant No. 2021-165). Shanxi Province Basic Research Program (Free Exploration) Surface Project (Grant No: 202303021221189). Science and research fund of Shanxi Health Commission (Grant No. 2019059, 2022042, 2022043). Shanxi Province “136 Revitalization Medical Project Construction Funds”. Shanxi Province Science Foundation for Distinguished Young Scholar (Grant No. 201901D211547). National Natural Science Foundation of China for Young Scholars (Grant No. 81201810). The doctor project of Shanxi Cancer Hospital, China (2017A06). Natural Science Foundation of Guangdong Province, China (2015A030313057). Research and Innovation Team Project for Scientific Breakthroughs at Shanxi Bethune Hospital (2024ZHANCHI07). The Science and Education Cultivation Fund of the National Cancer and Regional Medical Center of Shanxi Provincial Cancer Hospital (QH2023027).