bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2026–05–24
nine papers selected by
Maksym V. Kopanitsa, Charles River Laboratories



  1. Cell. 2026 May 19. pii: S0092-8674(26)00505-2. [Epub ahead of print]
      Sensory innervation regulates lung physiology and pathology, but its role in lung cancer is poorly understood. We show that lung adenocarcinoma (LUAD) progression locally amplifies nociceptive sensory innervation and activation, which drives the release of a major sensory neuropeptide, calcitonin gene-related peptide (CGRP). CGRP acts on a subset of macrophages, thereby impairing the recruitment of CXCL13+ fibroblasts and blocking tertiary lymphoid structure (TLS) assembly, a key predictor of LUAD prognosis. Local sensory denervation restores TLS formation, enhances B and T cell-dependent immunity, and suppresses tumor growth. Cigarette smoke extract (CSE) further activates this neural circuit to accelerate LUAD progression. In CSE-exposed animals, pharmacologic CGRP blockade sensitizes tumors to immunotherapy and prolongs survival. Together, our findings uncover a neuroimmune axis linking nociceptive neurons, TLS, and LUAD and identify neurogenic inflammation as a mechanism by which smoking promotes lung tumorigenesis independent of somatic mutagenesis.
    Keywords:  CGRP; cancer immunology; cancer neuroscience; chemogenetics; cigarette smoking; genetically engineered mouse model; lung adenocarcinoma; macrophage; neuroimmune crosstalk; non-small cell lung cancer; sensory neuron; tertiary lymphoid structure
    DOI:  https://doi.org/10.1016/j.cell.2026.04.038
  2. Cell Commun Signal. 2026 May 16.
      Colorectal cancer (CRC) is a major cause of cancer-related mortality worldwide, traditionally attributed to genetic mutations and epigenetic alterations. However, with the emergence of cancer neuroscience, a paradigm shift has occurred, revealing the central role of the nervous system in the initiation, progression, and metastasis of CRC. The gastrointestinal tract, being the only organ in the body with an independent peripheral nervous system - the enteric nervous system (ENS) - provides a unique anatomical and functional basis for neuro-tumor interactions. This review systematically explores the mechanisms by which the nervous system regulates CRC cell proliferation, invasion, and immune microenvironment remodeling through neurotransmitters (such as norepinephrine and acetylcholine) and neurotrophic factors (including NGF and BDNF). We also delve into the role of the brain-gut-microbiome axis, particularly its influence on tumor progression through metabolic reprogramming and neuroimmune crosstalk. Finally, we discuss novel therapeutic strategies based on the bidirectional communication between the nervous system and CRC, offering new perspectives for precise interventions in CRC.
    Keywords:  Colorectal cancer; Enteric nervous system; Immune response; Nervous system; Targeted therapy
    DOI:  https://doi.org/10.1186/s12964-026-02938-5
  3. Abdom Radiol (NY). 2026 May 22.
       OBJECTIVE: Perineural invasion (PNI) is an adverse feature in cervical cancer and may influence nerve-sparing surgery. We compared conventional radiomics and VGG-SAM deep-learning strategies for MRI-based preoperative prediction of PNI.
    METHODS: A retrospective cohort of 103 patients with cervical cancer, including 82 PNI-negative and 21 PNI-positive patients, was analyzed. PyRadiomics features were extracted from raw DICOM MRI and paired tumor masks. Four deep variants were evaluated: VGG only, SAM only, VGG + SAM naive fusion, and VGG + SAM learnable fusion. Patient-level stratified five-fold cross-validation was used. Primary metrics were sensitivity, specificity, balanced accuracy, F1-score, ROC-AUC, and PR-AUC. Uncertainty for the naive-versus-learnable comparison was assessed with 10,000 paired bootstrap resamples and exact McNemar tests.
    RESULTS: The strongest radiomics baseline, PyRadiomics + XGBoost, achieved balanced accuracy 0.6057, F1-score 0.3684, ROC-AUC 0.6731, and PR-AUC 0.4460. Naive VGG + SAM fusion achieved the best sensitivity (0.5714), balanced accuracy (0.7491), F1-score (0.6154), ROC-AUC (0.7854), and PR-AUC (0.6231). Learnable fusion achieved the highest specificity (0.9634) and precision (0.7500) while matching the highest accuracy (0.8544). Paired bootstrap comparisons showed wide confidence intervals across clinically relevant metrics.
    CONCLUSION: Hybrid VGG-SAM modeling outperformed conventional radiomics alone, but greater fusion complexity did not yield uniform benefit. Naive fusion favored sensitivity-oriented discrimination, whereas learnable fusion mainly shifted the operating point toward higher specificity. Larger multi-institutional cohorts and clinical comparators are needed.
    Keywords:  Cervical cancer; Deep learning; MRI; Perineural invasion; Predictive model; Radiomics
    DOI:  https://doi.org/10.1007/s00261-026-05559-1
  4. Mol Aspects Med. 2026 May 22. pii: S0098-2997(26)00043-9. [Epub ahead of print]110 101487
      Cancer transcends a local disease by engaging in systemic crosstalk with the host's physiology. This review redefines the vagus nerve as a central bioelectric processor within a dynamic brain-body-tumor homeostatic network, orchestrating a complex biological dialogue between them. We synthesize evidence illustrating its specialized architecture for encoding tumor microenvironment signals across metabolic, immune, and endocrine interfaces. Functioning as a dynamic, context-dependent integrator, it maintains systemic homeostasis while paradoxically being susceptible to hijacking by tumors, underscoring its dual role as both guardian and accomplice in cancer progression. This mechanistic framework paves the way for novel therapeutic reprogramming strategies. We explore the potential of precision bioelectronic neuromodulation, pharmacological interception of neural signaling, and behavioral interventions to "hack" this dialogue, aiming to enhance anti-tumor defenses, alleviate cancer-related symptoms, and synergize with conventional therapies. Future success hinges on deciphering the vagal neural code and developing personalized, ethically sound applications.
    Keywords:  Bioelectricity; Cancer neuroscience; Neuroimmunology; Neuromodulation
    DOI:  https://doi.org/10.1016/j.mam.2026.101487
  5. Clin Exp Med. 2026 May 20.
      Per- and polyfluoroalkyl substances (PFAS) are persistent pollutants linked to breast cancer (BC), but their role in perineural invasion (PNI) of triple-negative breast cancer (TNBC) is unclear. Cathepsin D (CTSD), a lysosomal protease, is hypothesized to mediate PFAS-induced PNI, though systematic evidence is lacking. We integrated multi-omics data from TCGA-BRCA, METABRIC, and single-cell RNA-seq datasets. Analyses included differential gene expression, Mendelian randomization, consensus clustering, and machine learning for prognostic modeling. Single-cell analyses were performed using Seurat, Monocle2, and CellChat. GraphBan screened natural CTSD-binding compounds, with binding affinity evaluated by molecular docking and dynamics simulations. Experimental validation included immunohistochemistry, immunofluorescence, Transwell, and Western blot assays. We identified 5 PFAS-associated PNI-related genes (PPGs), with CTSD central to TNBC PNI. PPG-based molecular subtyping revealed a high-risk subgroup exhibiting enhanced epithelial-mesenchymal transition (EMT) activity, proliferation capacity, and significantly poorer overall survival. The PPG-based prognostic model effectively stratified patient outcomes and immunotherapy response. Mendelian randomization confirmed a causal link between genetically predicted CTSD levels and BC risk. Single-cell analysis showed CTSD specifically enriched in myeloid cells; CTSD⁺ myeloid cells displayed immunosuppressive signatures and therapy resistance. CTSD⁺ epithelial cells interacted with cancer-associated fibroblasts via FGF signaling and showed altered metabolism. GraphBan predicted and experiments confirmed Aurantio-obtusin as a high-affinity CTSD inhibitor. Molecular simulations demonstrated stable binding of both PFAS and Aurantio-obtusin to CTSD. Histologically, elevated CTSD expression co-localized with CD68⁺ macrophages in PNI-positive TNBC tissues, while Aurantio-obtusin suppressed CTSD expression and inhibited TNBC cell proliferation and migration. This study suggests that PFAS exposure is associated with PNI and malignant progression in TNBC, potentially involving dysregulation of CTSD. The robust PPG-based prognostic signature and the natural inhibitor Aurantio-obtusin offer novel biomarkers and a potential therapeutic strategy for mitigating PFAS-related cancer risks.
    Keywords:  Cathepsin D; PFAS; Perineural invasion; Single-cell RNA sequencing; Triple-negative breast cancer; Tumor microenvironment
    DOI:  https://doi.org/10.1007/s10238-026-02164-w
  6. Neuro Oncol. 2026 May 19. pii: noag110. [Epub ahead of print]
      Brain metastases are a prevalent disease found in up to 40% of patients with solid cancers, and are associated with significant morbidity and mortality. Current treatment options for brain metastases are limited, especially because the tumor is protected by the blood-tumor barrier that prevents the penetration of chemotherapeutic agents. Understanding the brain metastatic process and the cells involved is required to discover new treatment approaches. One interesting therapeutic target is mural cells called pericytes, given their importance in maintaining the blood-brain barrier, regulating blood flow, modulating the immune response, and promoting angiogenesis in normal brain physiology. The role of cerebral pericytes in the initiation and maintenance of brain metastases is not well understood. In this review, we discuss the current understanding of the steps in the metastatic process and the roles of cerebral pericytes at each step, especially premetastatic niche formation, cancer cell extravasation, brain micrometastasis formation, and maintenance of macrometastasis and the tumor microenvironment. This study aims to provide a comprehensive understanding of the importance of brain pericytes in brain metastasis formation and maintenance, offer a perspective on the further investigations that are needed, and propose possible clinical implications for the treatment of brain metastases.
    Keywords:  brain metastasis; pericytes; premetastatic niche; tumor microenvironment
    DOI:  https://doi.org/10.1093/neuonc/noag110
  7. Surgery. 2026 May 02. pii: S0039-6060(26)00229-1. [Epub ahead of print]196 110304
       BACKGROUND: Stage III rectal cancer prognosis remains challenging despite therapeutic advances. This study investigates the combined prognostic value of perineural invasion and lymph node ratio, 2 established markers that have not been studied synergistically.
    METHODS: Retrospective analysis of 3,881 patients from the Surveillance, Epidemiology, and End Results database (training cohort) and 498 patients from 2 Chinese hospitals (validation cohort). Cox regression identified prognostic factors, and a subsequent nomogram was developed for 3-/5-year cancer-specific survival.
    RESULTS: Perineural invasion-positive patients showed significantly lower 3-year (74.7% vs 86.7%) and 5-year cancer-specific survival (61.7% vs 76.0%) than perineural invasion-negative counterparts (P < .0001). Lymph node ratio stratification revealed that perineural invasion had a stronger prognostic impact in the lymph node ratio ≤0.5 subgroups. The integrated nomogram incorporating perineural invasion, lymph node ratio, tumor grade, carcinoembryonic antigen status, and treatment parameters demonstrated high accuracy (area under the curve, 0.764-0.839) with excellent calibration.
    CONCLUSION: Perineural invasion and lymph node ratio synergistically predict survival in stage III rectal cancer. The validated nomogram provides a practical tool for individualized prognosis assessment and therapeutic decision-making, addressing current gaps in risk stratification.
    DOI:  https://doi.org/10.1016/j.surg.2026.110304
  8. JCI Insight. 2026 May 22. pii: e199498. [Epub ahead of print]11(10):
      Brain metastases (BrMs) occur in approximately 30% of cancer patients, causing nearly one-fifth of cancer deaths. While immune checkpoint inhibitors (ICIs) benefit some BrM patients, responses remain highly variable. This variability partly reflects distinct histopathological growth patterns that include minimally invasive (MI) and highly invasive (HI) brain BrMs. Here we show that MI BrMs exhibit robust immune infiltration, whereas HI lesions are immunosuppressed. However, histological differentiation between MI and HI can be challenging because of subjective margin assessment. Here, using highly multiplexed spatial proteomics on 119 tumor sections from 46 patients with BrMs, we identify CHI3L1 as a key mediator of the immunosuppressive microenvironment in HI BrMs. In preclinical models, genetic deletion of CHI3L1 converts immune-cold metastases into lymphocyte-rich, ICI-responsive lesions infiltrated by granzyme B+ CD8+ T cells. In BrM patients treated with ICI, immunohistochemical quantification of CHI3L1 expression was a stronger predictor of ICI response than traditional MI/HI classification. Thus, CHI3L1 represents a promising biomarker and therapeutic target for BrMs.
    Keywords:  Brain cancer; Immunology; Oncology
    DOI:  https://doi.org/10.1172/jci.insight.199498
  9. Mater Today Adv. 2026 Jun;pii: 100770. [Epub ahead of print]30
      Recapitulation of the complex nerve-tumor-immune microenvironment is critical for understanding Peripheral Nerve Sheath Tumors (PNSTs). Conventional in vitro models and animal systems often struggle to model crucial intercellular and inter-organ communication with full physiological relevance, creating a bottleneck in discovering effective therapeutics. Organ-on-Chip (OoC) technologies offer a paradigm-shifting solution. These microengineered platforms precisely integrate human cell biology with controllable fluidic and mechanical cues to replicate tissue- and organ-level physiology, enabling real-time, quantitative monitoring of tissue dynamics. This review posits that OoC technology is poised to revolutionize PNST research. In this review, we summarize the development of advanced Tumor-Nerve-Immune-on-Chip systems that integrate patient-derived Schwann cells, immune components, and functional microvasculature. These systems will accurately model PNSTs. Adoption of OoC will enable a predictive and individualized experimental framework, accelerating therapeutic discovery and allowing for personalized drug prediction for these challenging diseases.
    Keywords:  Disease modeling; Microfluidics; Organ-on-Chip; Peripheral nerve sheath tumor; Translational research
    DOI:  https://doi.org/10.1016/j.mtadv.2026.100770