Your new experience awaits. Try the new design now and help us make it even better

REVIEW article

Front. Immunol.

Sec. Cancer Immunity and Immunotherapy

This article is part of the Research TopicNeural influences on tumor immunity: Exploring neuroimmunology in cancerView all 24 articles

The Neuro-Immune Axis in Cancer: Mechanisms of Innervation-Driven Tumor Progression and Therapeutic Opportunities

Provisionally accepted
Liang  ZhangLiang ZhangDantong  ZhuDantong ZhuJunyi  WangJunyi WangJiyang  GuoJiyang GuoMingzhe  JiangMingzhe JiangXinhui  QiXinhui QiZhendong  ZhengZhendong Zheng*
  • Department of Oncology,General Hospital of Northern Theater Command, Shenyang, China

The final, formatted version of the article will be published soon.

Innervation plays a key role in tumor progression, and malignant tumor cells often invade peripheral nerve or the central nervous system, significantly altering tumor biological function. In this review, the multi-dimensional role of innervation in cancer biology is comprehensively discussed, the molecular mechanisms involved and their effects on the tumor microenvironment are deeply analyzed, and therapeutic strategies are proposed. We systematically summarize the interactions between cancer cells and neural tissue, focusing on how key signaling pathways regulate the core elements of this process. The analysis focused on the pathological features of innervation in specific cancer types, particularly breast, pancreatic, and prostate cancers, revealing the unique mode of action of innervation in these cancers. In addition, we explored the combined effects of innervation on the tumor microenvironment, including immune cell infiltration, angiogenesis, metabolic reprogramming, and the development of cancer-related pain. Together, these changes promote tumor growth and spread, further highlighting the importance of innervation in tumor progression. Finally, this review proposes the potential therapeutic value of innervation in the treatment of cancer, and aims to promote the development of the field of innervation research. A deeper understanding of the complex relationship between innervation and cancer progression is critical to optimizing treatment strategies, improving patient outcomes, and expanding the boundaries of our understanding of cancer biology.

Keywords: Angiogenesis, cancer-associatedaxons, innervation, therapeutic strategies, Tumor biology, Tumor Microenvironment

Received: 27 Aug 2025; Accepted: 19 Dec 2025.

Copyright: © 2025 Zhang, Zhu, Wang, Guo, Jiang, Qi and Zheng. 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: Zhendong Zheng

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.