ArticleJournal of experimental & clinical cancer research : CR2025
Peripheral nerve injury-induced remodeling of the tumor-associated macrophages promotes immune evasion in breast cancer.
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- RNF180 loss stabilizes BCAS4 to enhance PD-L1 expression and immune evasion in hepatocellular carcinoma.iScience · 2026Article
- Integrating single-cell and spatial transcriptomics to dissect mast-cell heterogeneity and arginine-metabolism-associated markers in BRCA.Neoplasia (New York, N.Y.) · 2026Article
- The Neuro-Bone Axis in Metastatic Progression: Innervation, Neuro-Immune-Osteoclast Crosstalk, and Therapeutic Opportunities.Biology · 2026Review
- Neural regulation of immune evasion in breast cancer: a multiscale neuro-immune framework.Frontiers in immunology · 2026Review
- Peripheral Nerve-Cancer Interactions in the Tumor Microenvironment: A Three-Dimensional Framework Integrating Mechanisms, Modulators, and Therapeutic Strategies.Research (Washington, D.C.) · 2026Review
- Neuro-immune crosstalk in breast cancer: molecular mechanisms from stress signals to immune escape.Frontiers in immunology · 2026Review
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Authors and funding
22 authors.
Funding
Abstract
backgroundPeripheral nerve damage is intricately linked to the progression of various solid tumors. However, its effect on antitumor immunity and precise underlying mechanisms remain poorly understood. This study aimed to elucidate the effect of peripheral nerve damage and its subsequent immune-modulating effects influence on breast cancer progression.
methodsWe analyzed nerve injury markers in the TCGA-BRCA database and clinical samples. In vivo experiments were conducted using orthotopic breast cancer models with chemical sympathetic denervation (6-OHDA) or nerve lysate/neurofilament light chain (NFL) treatment, where NFL was identified as a key effector molecule through mass spectrometry screening. The tumor microenvironment was evaluated by flow cytometry, multiplex immunohistochemistry, and single-cell RNA sequencing. In vitro co-culture systems were established to investigate the effects of NFL on macrophages and CD8
resultsPeripheral nerve injury was associated with poor prognosis and immune evasion in breast cancer patients. In mouse models, chemical sympathectomy (6-OHDA) and nerve lysates injection both accelerated tumor growth, suggesting that nerve damage promotes immune escape. Single-cell RNA sequencing (scRNA-seq) further revealed that nerve injury increased tumor-associated macrophages (TAMs) proportion by promoting TAMs proliferation and attracting macrophages. The key effector molecule of nerve lysates neurofilament light chain (NFL) was identified with the TAMs proliferation effect, and intratumoral NFL administration recapitulated the pro-tumor effects of nerve damage and perfomed the same immune-modulating effects as 6-OHDA and nerve lysates. Importantly, NFL-induced TAM enrichment and remodeling promoted CD8
conclusionThese findings underscore the critical role of peripheral nerve injury in reshaping the interplay between TAMs and antitumor immunity, via NFL-driven NF-κB activation and T cell dysfunction. Suggesting that neuroprotection could serve as a promising strategy to restore anticancer immunosurveillance.
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