Tumour innervation as a regulatory layer of cancer immunity

Denian Wang; Zhen Fu; Zhi Yang; Hao Liu; Qingyan Li; Daxing Zhu; Weimin Li

doi:10.59717/j.xinn-oncol.2026.100010

The Innovation Oncology > 2026 Vol. 1 > No. 1 > 100010

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Tumour innervation as a regulatory layer of cancer immunity

1.
Precision Medicine Research Center, West China Hospital, Sichuan University, Chengdu 610041, China
2.
Respiratory Health and Multimorbidity Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
3.
Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu 610041, China
4.
Research Units of West China, Chinese Academy of Medical Sciences, West China Hospital, Chengdu 610041, China
5.
West China College of Basic Medicine and Forensic Medicine, Sichuan University, Chengdu 610041, China
6.
Department of Nephrology, West China Hospital, Sichuan University, Chengdu 610041, China
7.
Department of Neurosurgery, West China Hospital, Sichuan University, Chengdu 610041, China
8.
Lung Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China
9.
These authors contributed equally

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Corresponding authors: weimi003@scu.edu.cn (W.L.); wangdenian623@wchscu.edu.cn (D.W.）
Received Date: April 22, 2026

Accepted Date: April 23, 2026

Published Online: April 25, 2026

The Innovation Oncology 1(1), https://doi.org/10.59717/j.xinn-oncol.2026.100010 | Cite this article

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Tumor innervation is a key regulator of the tumor microenvironment (TME) and affects cancer immunity.
  
  Neurotransmitters and neuropeptides shape immune cell function, forming a neuro–immune–metabolic axis.
  
  Neural signals interact with oncogenic pathways and exhibit marked heterogeneity within the TME.

ABSTRACT

ABSTRACT

Tumour immune regulation has traditionally been interpreted through immune cell states, metabolic reprogramming, and genomic alterations. Although this framework has advanced cancer immunology, it does not fully explain the marked heterogeneity of the tumour immune microenvironment or the poor response of many immunologically “cold” tumours to immune checkpoint blockade. Emerging evidence identifies the nervous system as an important but underappreciated regulator of tumour immunity. Many solid tumours are densely innervated by sympathetic, parasympathetic, and sensory nerves, and increased neural fiber density is frequently associated with immunosuppression, tumour progression, and metastasis. Through predominantly non-synaptic signalling, neurotransmitters and neuropeptides modulate immune cell recruitment, T cell activity, myeloid polarization, and immune tolerance within the tumour microenvironment. Neural signals also reshape tumour metabolism, establishing a neuro–immune–metabolic axis that converts transient neural inputs into sustained immunosuppressive states and self-reinforcing feedback loops linked to therapeutic resistance. At the systemic level, the central nervous system further influences tumour immunity through stress-related neuroendocrine pathways and behavioral states. In this Review, we summarize current knowledge on tumour innervation, neuro–immune crosstalk, and their metabolic basis, and discuss how neural regulation may shape immunotherapy responses and offer new opportunities for precision immunomodulation in cancer.
- tumour innervation /
- neuro-immune interactions /
- tumour immune microenvironment /
- neurotransmitters and neuropeptides /
- immunotherapy response heterogeneity.

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Wang D., Fu Z., Yang Z., et al. (2026). Tumour innervation as a regulatory layer of cancer immunity. The Innovation Oncology 1:100010. https://doi.org/10.59717/j.xinn-oncol.2026.100010

Wang D., Fu Z., Yang Z., et al. (2026). Tumour innervation as a regulatory layer of cancer immunity. The Innovation Oncology 1:100010. https://doi.org/10.59717/j.xinn-oncol.2026.100010

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Tumour innervation as a regulatory layer of cancer immunity

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