Li ZK, Liao JL, Luo MR, Fang SJ, Huang WZ, Zhang DY. Neuro-tumor interactions: Multi-dimensional mechanisms of neurotransmitter regulation in tumor immune evasion and metabolic reprogramming. World J Clin Oncol 2025; 16(10): 108954 [DOI: 10.5306/wjco.v16.i10.108954]
Corresponding Author of This Article
Dong-Yan Zhang, Research Fellow, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou 510515, Guangdong Province, China. 15013091401@163.com
Research Domain of This Article
Oncology
Article-Type of This Article
Minireviews
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Ze-Kai Li, Jia-Lin Liao, Min-Rui Luo, Shu-Jie Fang, Dong-Yan Zhang, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China
Wei-Zhen Huang, The Second Department of Oncology, The First Huizhou Affiliated Hospital of Guangdong Medical University, Huizhou 516000, Guangdong Province, China
Co-corresponding authors: Wei-Zhen Huang and Dong-Yan Zhang.
Author contributions: Li ZK conceptualized the topic and drafted the original manuscript; Liao JL and Luo MR performed literature review and data collection; Fang SJ contributed to the critical revision of the manuscript; Huang WZ and Zhang DY supervised the work and revised the manuscript for important intellectual content, and they contributed equally to this article as the co-corresponding authors of this manuscript; and all authors have read and approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 82272719; the Natural Science Foundation of Guangdong Province, No. 2023A1515012724 and No. 2024A1515013249; and the Science and Technology Projects in Guangzhou, No. 2024A04J5205.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: Dong-Yan Zhang, Research Fellow, Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, No. 1838 North Guangzhou Avenue, Guangzhou 510515, Guangdong Province, China. 15013091401@163.com
Received: April 27, 2025 Revised: June 2, 2025 Accepted: September 17, 2025 Published online: October 24, 2025 Processing time: 180 Days and 20.7 Hours
Abstract
Neurotransmitter-mediated regulation plays a multi-dimensional role in the tumor microenvironment, profoundly influencing key processes such as tumor immune evasion, metabolic reprogramming, and metastasis. However, the upstream regulatory mechanisms linking neural inputs to immune evasion and metabolic reprogramming remain incompletely understood. We systematically summarize current evidence from molecular, cellular, and immunological studies to elucidate how neurotransmitter-dependent mechanisms drive dynamic changes in the tumor microenvironment through the regulation of tumor cells and immune cells, and map the complex interaction networks between the nervous system and tumor progression. We propose a unifying “neuro-metabolic-immune axis” framework that highlights the dual role of neurotransmitters in suppressing anti-tumor immunity and facilitating tumor adaptation. By mapping this axis, we reveal new insights into tumor ecology and identify neural pathways as promising therapeutic targets. Targeting these pathways may enhance immunotherapy and disrupt tumor-supportive metabolism, offering new directions in precision oncology.
Core Tip: This article presents a novel perspective on the role of neural signaling in orchestrating tumor progression through the neuro-metabolic-immune axis within the tumor microenvironment. It illustrates that neurotransmitters can directly regulate immune evasion while also mediating metabolic reprogramming, thereby indirectly facilitating immunosuppression. This integrative framework unveils a dynamic bidirectional network wherein neural signals coordinate both metabolic and immune adaptations, offering new therapeutic targets aimed at disrupting this axis to enhance conventional cancer treatments.
