bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2026–07–12
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.
  2. Regulation of solid tumors by the peripheral nervous system.
  3. Clinicopathological significance of nerve density and perineural invasion in esophageal squamous cell carcinoma: A retrospective study with neuropeptide Y.
  4. Neural regulation of tumor progression: implications for hepatocellular carcinoma.
  5. Retraction: Promotion of perineural invasion of cholangiocarcinoma by Schwann cells via nerve growth factor.
  6. Neuron-tumor communication in solid tumors: from bona fide synapses to pseudo-synaptic neural interfaces.
  7. Culturing Primary Adult Mouse Dorsal Root Ganglion Neurons for Assessing Neuronal Function Following Treatment with Tumor Cell-Conditioned Medium.
  8. Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.
  1. Front Immunol. 2026 ;17 1729908
    Neuro-immune interactions in cancer: mechanisms and therapeutic prospects.
    Jingting Liu, Chun Zhang, Chong Zhang, Jianying Pei, Yan Li.
      The interplay between the nervous and immune systems has attracted growing scientific attention due to its implications for tumor progression, immune regulation, and potential therapeutic strategies. Although their primary concentration is on inflammation and homeostasis, this basic information emphasizes the crucial role that neuro-immune interaction plays in disease states, including cancer. Neuro-immune interactions are complex and multifaceted, playing significant effects on the pathophysiology of cancer. These interactions involve both peripheral and central neural pathways, modulating immune cell activity within the tumor microenvironment, and offering promising avenues for innovative therapeutic interventions. This review synthesizes recent advancements in understanding the molecular mechanisms, regulatory pathways, and translational applications of the neuro-immune axis in cancer. We explore the intricate roles of neurotransmitters, cytokines, and neurotrophic factors in mediating this crosstalk, examining how the peripheral, central, and enteric nervous systems regulate tumor immunity. Furthermore, we explore emerging therapeutic strategies that target neural inputs, combine neuroimmune modulation with immunotherapy, and consider the impact of epigenetic regulation on the neuroimmune microenvironment. By synthesizing recent advances, this review aims to provide a comprehensive understanding of this intricate field, identify current challenges, and delineate future research directions to harness neuro-immune modulation for offering promising avenues for innovative therapeutic interventions.
    Keywords:  cancer; immune systems; nervous system; neuro-immunity; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1729908
  2. J Exp Med. 2026 Aug 03. pii: e20251333. [Epub ahead of print]223(8):
    Regulation of solid tumors by the peripheral nervous system.
    Aeson Chang, Shenghong Zhu, Terrance Lam, Erica K Sloan.
      The nervous system has emerged as a critical regulator of cancer progression. Recent studies demonstrate that peripheral neurons shape tumor growth, dissemination, and therapeutic response by regulating multiple components of the tumor microenvironment. In parallel, tumors within the body remodel their neural niche by recruiting innervation and modulating neuronal phenotype and activity. This bidirectional cross talk positions neural circuits as integral components of the tumor ecosystem, linking environmental cues, including metabolic stress, inflammation, and the impact of treatment, to coordinated multicellular responses that promote progression and treatment resistance. Here, we review the field of cancer neuroscience with a focus on solid tumors originating outside the central nervous system. We synthesize mechanistic insights into how the peripheral nervous system shapes the tumor microenvironment to influence tumor behavior and highlight emerging therapeutic opportunities to target neural pathways. Together, these findings identify the nervous system as an upstream regulator of cancer biology and a tractable target for intervention.
    DOI:  https://doi.org/10.1084/jem.20251333
  3. Pathol Res Pract. 2026 Jul 06. pii: S0344-0338(26)00269-4. [Epub ahead of print]286 156616
    Clinicopathological significance of nerve density and perineural invasion in esophageal squamous cell carcinoma: A retrospective study with neuropeptide Y.
    Ruibing Su, Danwei Zheng, Yuanning Guo, Shaobin Chen, Haihua Huang, Dongping Tian, Wei Wang, Min Su.
      The clinicopathological and prognostic implications of neural involvement, including nerve density (ND) and perineural invasion (PNI), in esophageal squamous cell carcinoma (ESCC) remain incompletely understood. This retrospective study aimed to evaluate ND and PNI using neuropeptide Y (NPY) in 201 patients with ESCC. Scoring methods for ND and PNI were applied based on digital slicing, and Receiver Operating Characteristic (ROC), Kaplan-Meier curves, and Cox regression were used for survival analysis and to explore the association between ND/PNI and clinicopathological features. ROC analyses showed slightly higher AUCs for ND compared with PNI-related indicators in predicting overall survival (OS) and disease-free survival (DFS), without statistical significance. Kaplan-Meier curves and Cox model demonstrated that ND was a significant factor influencing survival prognosis [Hazard Ratio (HR) = 2.065, 95% confidence interval (CI) 1.384-3.080, P < 0.001 for OS; HR = 1.929, 95% CI 1.198-3.108, P = 0.007 for DFS]. Multivariate analysis indicated that ND was independently associated with OS (HR = 2.131, 95% CI 1.418-3.021, P < 0.001) and DFS (HR = 1.818, 95% CI 1.112-2.972, P = 0.017). Notably, the adverse prognostic impact of high-level ND was primarily observed among patients with lymph node metastasis (pN+) for both OS and DFS. In this pN+ subgroup, NII (HR = 2.203, P = 0.022) and PNI status (HR = 1.985, P = 0.048) were independently associated with DFS, whereas NISS (HR = 1.821, P = 0.086) did not reach statistical significance. In conclusion, NPY-based quantification of tumor-associated neural parameters-particularly ND-was associated with survival outcomes in ESCC. Overall, these results highlight the potential relevance of NPY-positive neural alterations in ESCC progression and support further investigation into their biological and prognostic roles within the tumor microenvironment.
    Keywords:  Cancer neuroscience; Esophageal squamous cell carcinoma; Nerve density; Neuropeptide Y; Perineural invasion; Prognosis
    DOI:  https://doi.org/10.1016/j.prp.2026.156616
  4. Front Immunol. 2026 ;17 1884297
    Neural regulation of tumor progression: implications for hepatocellular carcinoma.
    Yalin Chen, Zhanghui Long, Yuan-Sheng Zang, Dong Wu.
      The nervous system is increasingly recognized as an active regulator of oncogenesis rather than a passive structural component of the tumor microenvironment (TME). Neural activity promotes tumor proliferation, invasion, metastasis, therapeutic resistance and immune evasion through dynamic, bidirectional interactions with malignant cells and stromal components. These effects are mediated by diverse mechanisms, including synaptic and pseudo-synaptic communication, paracrine release of neurotransmitters and neuropeptides, metabolic reprogramming, and neuro-immune crosstalk. Importantly, tumors do not simply receive neural signals; they actively remodel the peripheral nervous system by inducing axonogenesis and neo-innervation, thereby establishing feed-forward circuits that facilitate disease progression. In hepatocellular carcinoma (HCC), central nervous system responses to systemic stress converge with local hepatic signaling to regulate tumor dynamics. Sympathetic, parasympathetic, and sensory innervation influence hepatocarcinogenesis by modulating inflammation, immunosuppression, stromal remodeling and cellular metabolism. These processes may contribute to the transition from chronic liver disease to malignant transformation. Although recent studies have demonstrated neuro-tumor crosstalk in HCC, critical knowledge gaps remain, including the precise neural circuits involved, the temporal dynamics of innervation during disease progression, and the intersection of these pathways with canonical oncogenic drivers. This review summarizes current knowledge of neural-mediated tumor progression across malignancies and discusses the relevance of these paradigms to HCC, with an emphasis on potential therapeutic vulnerabilities. A deeper mechanistic understanding of these processes is essential for translating neuro-oncological concepts into targeted neuromodulatory therapies for HCC.
    Keywords:  hepatocellular carcinoma; immunosuppression; neuro-tumor interactions; perineural invasion; tumor microenvironment
    DOI:  https://doi.org/10.3389/fimmu.2026.1884297
  5. J Gastrointest Oncol. 2026 Jun 30. 17(3): 203
    Retraction: Promotion of perineural invasion of cholangiocarcinoma by Schwann cells via nerve growth factor.
    Xingwang Qian, Enchi Liu, Chong Zhang, Ruo Feng, Nguyen Tran, Wenlong Zhai, Fazhan Wang, Zhihai Qin.
      [This retracts the article DOI: 10.21037/jgo-24-309.].
    DOI:  https://doi.org/10.21037/jgo-20262-03
  6. Trends Cancer. 2026 Jul 09. pii: S2405-8033(26)00136-6. [Epub ahead of print]
    Neuron-tumor communication in solid tumors: from bona fide synapses to pseudo-synaptic neural interfaces.
    Lei Ren, Chunfeng Liu, Wangsheng Chen, Yinchun Wang, Gerhard Rammes, Peter H Neckel, Andreas Klingl, Rouzanna Istvanffy, Helmut Friess, Güralp O Ceyhan, Qingqiang Yang, Ihsan Ekin Demir.
      Neuron-tumor communication is emerging as a distinct layer of tumor-host interaction beyond conventional stromal, vascular, and immune regulation. Recent studies show that malignant cells can detect neuronal activity and convert neural signals into growth-promoting cellular responses. In the brain, glioma cells can become electrically integrated into neuronal circuits, where glutamatergic input drives depolarization, calcium influx, and downstream signaling. In extracranial tumors, neural influence appears more heterogeneous, involving spatially organized neurochemical niches, receptor-enriched cancer-nerve contacts ('pseudo-synapses'), autonomic pathways, and injury-associated neuroimmune remodeling. These findings raise important questions about how neural input regulates tumor cell state, metabolism, immune tone, and therapeutic adaptation. This review evaluates the evidence linking neural activity to cancer progression across anatomical contexts and outlines the experimental standards needed to distinguish structured neuron-tumor interfaces from broader neural effects within the tumor microenvironment.
    Keywords:  cancer neuroscience; neural circuits; neuron–tumor communication; neuron–tumor synapse; pseudo-synaptic interface; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.trecan.2026.06.008
  7. J Vis Exp. 2026 Jun 22.
    Culturing Primary Adult Mouse Dorsal Root Ganglion Neurons for Assessing Neuronal Function Following Treatment with Tumor Cell-Conditioned Medium.
    Khalil Ali Ahmad Kasm, Sandeep Dembla, Angela C Hirbe, Andrew J Shepherd, Yuan Pan.
      Interactions between sensory neurons and tumor cells are increasingly recognized as critical contributors to tumor progression and cancer-associated pain. Here, we describe a reproducible protocol for the isolation and culture of adult mouse dorsal root ganglion (DRG) neurons, followed by functional and molecular assays to assess their responses to tumor-derived secreted factors. Adult DRG were dissected, enzymatically digested with Liberase DH, and dissociated into single neurons. The cells were plated on laminin-coated coverslips and maintained in defined culture conditions that promote neuronal survival while minimizing glial overgrowth. Subsequently, the cultured neurons were exposed to tumor cells' conditioned medium to model paracrine signaling at the neuron-tumor interface. Functional responses were monitored by live cell calcium imaging using fluorescent indicators, enabling quantification of neuronal activity and stimulus-specific responsiveness. In parallel, neuronal stress and injury are evaluated by ATF3 immunostaining. Together, these complementary approaches provide a powerful platform to investigate how tumor-secreted factors sensitize or activate sensory neurons. This protocol integrates adult DRG culture, tumor-conditioned medium treatment, calcium imaging, and molecular readouts into a single workflow, enabling researchers to dissect mechanisms of neuron-tumor communication. The method is broadly applicable to studies of cancer neuroscience, pain signaling, and the identification of secreted mediators that modulate neuronal function in disease contexts.
    DOI:  https://doi.org/10.3791/70748
  8. Cancer Res. 2026 Jul 09.
    Neurotropism and Therapeutic Targeting of Brain Metastases in Small Cell Lung Cancer.
    Triparna Sen, Elisa Gobbini, Khalis Mustafayev, Logan S Spiegelman, Fatma Nihan Akkoc Mustafayev, Fred R Hirsch, Asrar A Alahmadi, Manmeet S Ahluwalia.
      Small cell lung cancer (SCLC) is an aggressive malignancy marked by rapid progression, early dissemination, and a pronounced propensity for brain metastases (BM), which develop in up to 80% of patients. SCLC is defined by profound genomic instability, lineage plasticity, and rapid drug resistance. The establishment of BM is promoted by neuronal mimicry, enhanced intercellular adhesion, and dynamic crosstalk with astrocytes and microglia. Emerging therapies targeting DLL3 and B7H3 have demonstrated encouraging intracranial activity. Despite these advances, treatment resistance and limited brain drug penetration remain major unmet needs. This review highlights recent advances in SCLC BM biology and precision therapeutic strategies.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-25-5968
This page is being maintained by Thomas Krichel. It was last updated on 2026‒11‒11 at 0:17.