# The neuro-immune axis in cancer: mechanisms of innervation-driven tumor progression and therapeutic opportunities

**Authors:** Liang Zhang, Dantong Zhu, Junyi Wang, Jiyang Guo, Mingzhe Jiang, Xinhui Qi, Zhuo Zhang, Zhendong Zheng

PMC · DOI: 10.3389/fimmu.2025.1693419 · Frontiers in Immunology · 2026-01-12

## TL;DR

This review explores how nerve connections influence cancer progression and highlights new therapeutic opportunities based on these interactions.

## Contribution

The paper systematically summarizes the role of innervation in specific cancers and proposes new therapeutic strategies based on neuro-immune interactions.

## Key findings

- Innervation significantly alters tumor biological functions by interacting with cancer cells and neural tissue.
- Key signaling pathways regulate the interactions between cancer cells and nerves, affecting tumor progression.
- Innervation influences immune cell infiltration, angiogenesis, and cancer-related pain in the tumor microenvironment.

## Abstract

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.

## Linked entities

- **Diseases:** breast cancer (MONDO:0004989), pancreatic cancer (MONDO:0005192), prostate cancer (MONDO:0005159)

## Full-text entities

- **Diseases:** breast, pancreatic, and prostate cancers (MESH:C537243), pain (MESH:D010146), cancer (MESH:D009369)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

131 references — full list in the complete paper: https://tomesphere.com/paper/PMC12833073/full.md

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Source: https://tomesphere.com/paper/PMC12833073