Minireviews
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 107341
Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.107341
Role of interleukins in the pathogenesis of cholangiocarcinoma: A literature review
Saira Rafaqat, Hafsa Hamid, Roha Asif, Muhammad Asif, Maria Tariq, Malaika Saleem, Hijab Abaid
Saira Rafaqat, Department of Zoology, Lahore College for Women University, Lahore 54000, Pakistan
Hafsa Hamid, Roha Asif, Malaika Saleem, Department of Biotechnology, Lahore College for Women University, Lahore 54000, Pakistan
Muhammad Asif, Maria Tariq, Department of Zoology, University of Education, Lahore 54000, Punjab, Pakistan
Hijab Abaid, School of Biochemistry and Biotechnology, University of the Punjab, Lahore 54000, Punjab, Pakistan
Author contributions: Rafaqat S, Asif M, and Tariq M carried out the study design and data collection; Hamid H, Asif R, Saleem M, and Abaid H wrote the manuscript; Rafaqat S edited the manuscript; All authors read and approved the final manuscript.
Conflict-of-interest statement: There are no conflicts of interest associated with the senior author or other coauthors.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Saira Rafaqat, PhD, Department of Zoology, Lahore College for Women University, Jail Rd, Near Wapda Flats, Lahore 54000, Pakistan. saera.rafaqat@gmail.com
Received: March 21, 2025
Revised: April 27, 2025
Accepted: June 6, 2025
Published online: July 15, 2025
Processing time: 116 Days and 0.9 Hours
Abstract

This article summarized the role of interleukins (ILs) in the pathogenesis of cholangiocarcinoma (CCA). It discovered a negative feedback mechanism wherein alternative splicing led to the upregulation of the IL 1 receptor antagonist (IL1RN) isoforms IL1RN-201 and IL1RN-203, which play a crucial anti-inflammatory role in KRAS-mutant intrahepatic CCA (iCCA). Higher levels of IL-4 receptor were associated with a worse survival rate in patients with CCA. In addition, elevated levels of serum IL-6 have been associated with the start and progression of CCA, a common cancer generated by inflammation. IL-8 was a useful predictor of human hilar CCA. Mechanistically, signal transducer and activator of transcription 3 signaling was used by IL-10 produced from M2-polarized tumor-associated macrophages to enhance the malignant characteristics of iCCA cells. It was suggested that IL-17A and IL-22 have an impact on the development of CCA associated with hepatic fluke infection. The most significant finding was the decreased expression of the IL-23 receptor, a prognostic gene, in iCCA. IL-25 may be a useful prognostic biomarker as aberrant expression of the protein in CCA tissue was linked to tumor spread and a poor prognosis. Tumor cell migration and proliferation were both accelerated by homogenized liver tissue that expressed IL-33 significantly. The correlation between high IL-35 expression and aggressiveness in iCCA highlights it as a useful biomarker for assessing the course and prognosis of iCCA in clinical settings. This article concluded that IL-1, IL-4, IL-6, IL-8, IL-10, IL-17, IL-23, IL-25, IL-33, and IL-35 play significant roles in the pathogenesis of CCA. Further research is required to find the association of other ILs such as IL-2, IL-3, IL-5, IL-7, IL-11, and more in the pathogenesis of CCA.

Keywords: Cholangiocarcinoma; Intrahepatic cholangiocarcinoma; Interleukins; Pathogenesis

Core Tip: Interleukins (IL) contribute to cholangiocarcinoma (CCA) pathogenesis by promoting chronic inflammation, enhancing tumor cell survival, proliferation, and invasion, and shaping a tumor microenvironment that supports cancer growth and metastasis. ILs, which are a group of cytokines, play a crucial role in mediating the immune response and inflammation. This article concluded that IL-1, IL-4, IL-6, IL-8, IL-10, IL-17, IL-23, IL-25, IL-33, and IL-35 play significant roles in the pathogenesis of CCA. Further research is required to find the association of other ILs such as IL-2, IL-3, IL-5, IL-7, IL-11, and more in the pathogenesis of CCA.