Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications

Abstract The nervous system precisely regulates physiological activities throughout the body, controlling not only muscle movement, sensory perception, cognition, and responses to external stimuli but also the immune system. In the tumor microenvironment (TME), neural components are important consti...

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Main Authors: Tianyi Pu, Jiazheng Sun, Guosheng Ren, Hongzhong Li
Format: Article
Language:English
Published: Nature Publishing Group 2025-06-01
Series:Signal Transduction and Targeted Therapy
Online Access:https://doi.org/10.1038/s41392-025-02241-8
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author Tianyi Pu
Jiazheng Sun
Guosheng Ren
Hongzhong Li
author_facet Tianyi Pu
Jiazheng Sun
Guosheng Ren
Hongzhong Li
author_sort Tianyi Pu
collection DOAJ
description Abstract The nervous system precisely regulates physiological activities throughout the body, controlling not only muscle movement, sensory perception, cognition, and responses to external stimuli but also the immune system. In the tumor microenvironment (TME), neural components are important constituents that control the genesis, invasion, and metastasis of tumors by regulating the immune system. The nervous system modulates the tumor immune microenvironment (TIME) through localized control mechanisms (such as sensory, sympathetic, and parasympathetic innervation, as well as glial cell regulation) or via systemic adjustments, including circadian rhythm entrainment, stress modulation, and gut-brain axis regulation. To ensure their survival and proliferation, tumor cells can mimic the anti-inflammatory profiles of neuronal cells by expressing corresponding molecules to evade immune surveillance. Owing to these molecular similarities, the immune system’s targeted attack on the nervous system can lead to neurological damage, exacerbate patient conditions, and elevate mortality rates. Therefore, a detailed understanding of how the nervous and immune systems coordinate and regulate the TME can provide new perspectives and methods for the prevention and treatment of cancer. In this review, we focus on recent studies exploring the bidirectional interplay between the nervous system and tumors mediated by the immune system: how neural activity modulates tumor immunity, and conversely, how tumor-driven immune changes impact nervous system function.
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spelling doaj-art-d53bce091b7e42cf8d5e3f13f74228bd2025-08-20T02:31:09ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-06-0110113310.1038/s41392-025-02241-8Neuro-immune crosstalk in cancer: mechanisms and therapeutic implicationsTianyi Pu0Jiazheng Sun1Guosheng Ren2Hongzhong Li3Department of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Breast and Thyroid Surgery, Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical UniversityAbstract The nervous system precisely regulates physiological activities throughout the body, controlling not only muscle movement, sensory perception, cognition, and responses to external stimuli but also the immune system. In the tumor microenvironment (TME), neural components are important constituents that control the genesis, invasion, and metastasis of tumors by regulating the immune system. The nervous system modulates the tumor immune microenvironment (TIME) through localized control mechanisms (such as sensory, sympathetic, and parasympathetic innervation, as well as glial cell regulation) or via systemic adjustments, including circadian rhythm entrainment, stress modulation, and gut-brain axis regulation. To ensure their survival and proliferation, tumor cells can mimic the anti-inflammatory profiles of neuronal cells by expressing corresponding molecules to evade immune surveillance. Owing to these molecular similarities, the immune system’s targeted attack on the nervous system can lead to neurological damage, exacerbate patient conditions, and elevate mortality rates. Therefore, a detailed understanding of how the nervous and immune systems coordinate and regulate the TME can provide new perspectives and methods for the prevention and treatment of cancer. In this review, we focus on recent studies exploring the bidirectional interplay between the nervous system and tumors mediated by the immune system: how neural activity modulates tumor immunity, and conversely, how tumor-driven immune changes impact nervous system function.https://doi.org/10.1038/s41392-025-02241-8
spellingShingle Tianyi Pu
Jiazheng Sun
Guosheng Ren
Hongzhong Li
Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
Signal Transduction and Targeted Therapy
title Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
title_full Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
title_fullStr Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
title_full_unstemmed Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
title_short Neuro-immune crosstalk in cancer: mechanisms and therapeutic implications
title_sort neuro immune crosstalk in cancer mechanisms and therapeutic implications
url https://doi.org/10.1038/s41392-025-02241-8
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AT jiazhengsun neuroimmunecrosstalkincancermechanismsandtherapeuticimplications
AT guoshengren neuroimmunecrosstalkincancermechanismsandtherapeuticimplications
AT hongzhongli neuroimmunecrosstalkincancermechanismsandtherapeuticimplications