REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1621464
This article is part of the Research TopicTargeting tumor-initiating cells to enhance cancer immunotherapy in digestive system tumorsView all 8 articles
The lmmunomodulatory Role of Tumor-Initiating Cells in Digestive System Tumors: From Mechanisms to Therapy
Provisionally accepted
- 1School of Medicine, Yunnan University, Kunming, China, Kunming, China
- 2Yunnan Technological Innovation Centre of Drug Addiction Medicine, Yunnan University, Kunming, China, Kunming, China
- 3Department of Gastrointestinal and hernia surgery, the first affiliated Hospital of Kunming Medical University, Kunming, China, Kunming, China
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Targeting tumor-initiating cells (TICs) in digestive system tumors is a feasible strategy to boost the effectiveness of cancer immunotherapy. Because of their stem celllike properties, TICs can cause tumor heterogeneity, recurrence, and resistance to conventional medicines, which can seriously impair treatment outcomes. This review discusses the unique features of TICs inside various digestive system tumors, such as colorectal, pancreatic, liver, and gastric cancers. We look at the mechanisms that TICs evade immune recognition, including altered tumor microenvironment, decreased immunogenicity, and immune checkpoint molecule expression. Furthermore, we highlight potential strategies for TICs, such as differentiation therapies, inhibiting certain signaling pathways, and enhancing immune recognition through advanced immunotherapeutic approaches. The analysis also examines the potential for combination therapy, which include adoptive cell therapies, TIC-targeted strategies, and immune checkpoint inhibitors. Lastly, we address the challenges presented by TIC heterogeneity and immune escape mechanisms, emphasizing the need for more clinical research to back up these innovative tactics. All things considered, TIC targeting is a significant method to improve immunotherapy's efficacy in treating digestive system cancers, which will ultimately help patients.
Keywords: tumor-initiating cells (TICs), Digestive system tumors, Immunotherapy, Tumor Microenvironment, immune checkpoints, combination therapy, differentiation therapy
Received: 01 May 2025; Accepted: 08 Jul 2025.
Copyright: © 2025 Zhang, Zhang, Xu, Wang and Huang. 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:
Kunhua Wang, Yunnan Technological Innovation Centre of Drug Addiction Medicine, Yunnan University, Kunming, China, Kunming, China
Fang Huang, School of Medicine, Yunnan University, Kunming, China, Kunming, 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.