The neuro–metabolic–immune axis in breast cancer: emerging mechanisms and subtype-specific therapeutic opportunities
- 1Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
- 2School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, University of Hong Kong
Abstract
Tumor innervation is increasingly recognized as an active component of the breast tumor microenvironment, where neural signals influence cancer cells, stromal populations, and immune responses through neurotransmitters, neuropeptides, and neurotrophic factors. Sympathetic, cholinergic, and sensory pathways can regulate tumor growth, migration, stromal remodeling, and immune activity, while neural signaling also intersects with tumor metabolism by modulating glycolysis, lipid mobilization, and amino acid utilization. Metabolic changes, including lactate accumulation and histone lactylation, may further reshape tumor and immune-cell states, linking neural activity with metabolic adaptation and immune regulation. These interactions vary across breast cancer subtypes, with adrenergic and sensory-neuropeptide signaling implicated in triple-negative breast cancer, metabolic adaptation during HER2-targeted therapy, and neurotrophic and adipose-tumor crosstalk in hormone receptor-positive/HER2-negative disease. We apply the recently proposed concept of the neuro–metabolic–immune axis to breast cancer, systematically evaluating the strength of evidence for each component and organizing the discussion by molecular subtype and therapeutic maturity. We further discuss therapeutic opportunities ranging from β-adrenergic and neuropeptide pathway modulation to downstream metabolic targeting, while distinguishing direct neural mechanisms from indirect or complementary evidence.
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BibTeX
@article{xia2026neurometabolicimmune,
title = {{The neuro–metabolic–immune axis in breast cancer: emerging mechanisms and subtype-specific therapeutic opportunities}},
author = {Nannan Xia and Renhong Huang and Hanyi Zhong and Ziling Zhou and Shoutang Wang and Zheng Wang and Kunwei Shen},
journal = {Frontiers in Immunology},
year = {2026},
month = oct,
doi = {10.3389/fimmu.2026.1890810},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1890810/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The neuro–metabolic–immune axis in breast cancer: emerging mechanisms and subtype-specific therapeutic opportunities
AU - Nannan Xia
AU - Renhong Huang
AU - Hanyi Zhong
AU - Ziling Zhou
AU - Shoutang Wang
AU - Zheng Wang
AU - Kunwei Shen
PY - 2026
DA - 2026/10/19
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1890810
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1890810/full
AB - Tumor innervation is increasingly recognized as an active component of the breast tumor microenvironment, where neural signals influence cancer cells, stromal populations, and immune responses through neurotransmitters, neuropeptides, and neurotrophic factors. Sympathetic, cholinergic, and sensory pathways can regulate tumor growth, migration, stromal remodeling, and immune activity, while neural signaling also intersects with tumor metabolism by modulating glycolysis, lipid mobilization, and amino acid utilization. Metabolic changes, including lactate accumulation and histone lactylation, may further reshape tumor and immune-cell states, linking neural activity with metabolic adaptation and immune regulation. These interactions vary across breast cancer subtypes, with adrenergic and sensory-neuropeptide signaling implicated in triple-negative breast cancer, metabolic adaptation during HER2-targeted therapy, and neurotrophic and adipose-tumor crosstalk in hormone receptor-positive/HER2-negative disease. We apply the recently proposed concept of the neuro–metabolic–immune axis to breast cancer, systematically evaluating the strength of evidence for each component and organizing the discussion by molecular subtype and therapeutic maturity. We further discuss therapeutic opportunities ranging from β-adrenergic and neuropeptide pathway modulation to downstream metabolic targeting, while distinguishing direct neural mechanisms from indirect or complementary evidence.
SN - 1664-3224
ER -