ArticleJournal of experimental & clinical cancer research : CR2024
Mechanisms of neural infiltration-mediated tumor metabolic reprogramming impacting immunotherapy efficacy in non-small cell lung cancer.
Article in Journal of experimental & clinical cancer research : CR, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed.
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- The Role of the Nervous System in Lung Disease.Current neurology and neuroscience reports · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- The neural stem cell‑NSCLC axis: Molecular drivers, microenvironment crosstalk and emerging therapies (Review).International journal of oncology · 2026Review
- Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.MedComm · 2026Review
- Chemical Bond-Orchestrated Energy Depletion to Augment Lung Cancer Chemo-Immunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- Neural regulation of tumor immunity: emerging opportunities to enhance cancer immunotherapy.Experimental & molecular medicine · 2026Review
- An interpretable multi-task whole-slide histopathology AI model for non-small cell lung cancer: Cross-cohort generalisation, spatial attention-transcriptomic integration, and molecular-immune profiling.Clinical and translational medicine · 2026Article
- Wired for immunity: neuroimmune control of the lung by sensory neurons.Nature reviews. Neuroscience · 2026Review
- Neuro-immune crosstalk in the tumor microenvironment: mechanisms and therapeutic implications for cancer immunotherapy.Journal of neuroinflammation · 2026Review
- The role of γ-aminobutyric acid and its receptor in metabolic reprogramming and tumor progression.Biochemistry and biophysics reports · 2026Review
- Harnessing Gut Microbiota to Enhance Immunotherapy in NSCLC: From Mechanisms to Translational Applications.Cancer medicine · 2026Review
- Molecular mechanisms and therapeutic targets in lung cancer-nerve crosstalk.Chinese medical journal pulmonary and critical care medicine · 2026Review
- Single-Cell Atlas of Renal Cell Carcinoma Brain Metastasis Uncovers Mechanisms of Immune Dysfunction and Resistance.bioRxiv : the preprint server for biology · 2026Article
- USP7-dependent stabilization of FKBP4 contributes to acquired osimertinib resistance through glycolytic remodeling in NSCLC.Scientific reports · 2026Article
- Activation of Nerve Growth Factor signaling limits the response to lenvatinib in hepatocellular carcinoma.Signal transduction and targeted therapy · 2026Article
- Review
- Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Article
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
backgroundCurrent evidence underlines the active role of neural infiltration and axonogenesis within the tumor microenvironment (TME), with implications for tumor progression. Infiltrating nerves stimulate tumor growth and dissemination by secreting neurotransmitters, whereas tumor cells influence nerve growth and differentiation through complex interactions, promoting tumor progression. However, the role of neural infiltration in the progression of non-small cell lung cancer (NSCLC) remains unclear.
methodsThis study employs the techniques of immunohistochemistry, immunofluorescence, RNA sequencing, molecular biology experiments, and a murine orthotopic lung cancer model to deeply analyze the specific mechanisms behind the differential efficacy of NSCLC immunotherapy from the perspectives of neuro-tumor signal transduction, tumor metabolism, and tumor immunity.
resultsThis study demonstrates that nerve growth factor (NGF) drives neural infiltration in NSCLC, and 5-hydroxytryptamine (5-HT), which is secreted by nerves, is significantly elevated in tumors with extensive neural infiltration. Transcriptome sequencing revealed that 5-HT enhanced glycolysis in NSCLC cells. Pathway analysis indicated that 5-HT activated the PI3K/Akt/mTOR pathway, promoting tumor metabolic reprogramming. This reprogramming exacerbated immunosuppression in the TME. Neutralizing 5-HT-mediated metabolic reprogramming in tumor immunity enhanced the efficacy of PD-1 monoclonal antibody treatment in mice.
conclusionsThe findings of this study provide a novel perspective on the crosstalk between nerves and lung cancer cells and provide insights into further investigations into the role of nerve infiltration in NSCLC progression.
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