bims-netuvo 2026-05-03 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–05–03
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Halting neuron-fibroblast crosstalk disarms tumor and augments immunotherapy.
Peripheral nerves can serve as a sanctuary for lymphoma.
A local sympathetic-immune axis inhibits melanoma growth in mice by dictating adrenergic control.
Preoperative prediction of perineural invasion in pancreatic ductal adenocarcinoma using dual-layer spectral CT.
Prognostic significance of perineural invasion in esophageal squamous cell carcinoma: A large-scale propensity score matching analysis with long-term follow-up outcomes.
The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.
Neuroglial-Breast Cancer Crosstalk Shapes the Brain Metastatic Niche.
Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis.

Trends Pharmacol Sci. 2026 Apr 30. pii: S0165-6147(26)00080-5. [Epub ahead of print]

Halting neuron-fibroblast crosstalk disarms tumor and augments immunotherapy.

Pinchao Fan, Xiaofei Zhi, Weici Laurence Liu.

  Innervation propels tumor progression through intricate mechanisms. Recently, Zhang et al. demonstrated that sensory neurons interact with cancer-associated fibroblasts via the calcitonin gene-related peptide (CGRP)-receptor activity-modifying protein 1 (RAMP1) axis to mediate immune exclusion in triple-negative breast cancer. Halting the neuron-fibroblast crosstalk via rimegepant holds promise for reorganizing the extracellular matrix and synergizing with cancer immunotherapy.

Keywords:  breast cancer; cancer neuroscience; cancer-associated fibroblast; extracellular matrix; immunotherapy; tumor innervation

DOI:  https://doi.org/10.1016/j.tips.2026.03.006
Pract Neurol. 2026 Apr 28. pii: pn-2025-005041. [Epub ahead of print]

Peripheral nerves can serve as a sanctuary for lymphoma.

Felipe J S Jones, Robert J Spinner, JaNean Engelstad, Audrey M Blazek, Kimberly K Amrami, Marcus V Pinto.



Keywords:  LYMPHOMA; PERIPHERAL NERVE SURGERY; PERIPHERAL NEUROPATHOLOGY

DOI:  https://doi.org/10.1136/pn-2025-005041
Neuron. 2026 Apr 29. pii: S0896-6273(26)00285-0. [Epub ahead of print]

A local sympathetic-immune axis inhibits melanoma growth in mice by dictating adrenergic control.

Tingting Liu, Daniel Y Kutsovsky, Ethan M Earlie, Liangliang Ji, Michael Iskols, Shakti Ramsamooj, Xavier I Dawkins, Marwa Zerhouni, Alexander Birbrair, Elena Piskounova, Ming O Li, Ashley M Laughney, David J Simon.

  The nervous system drives tumor growth directly through intra-tumoral axons and indirectly through the systemic action of hormones. Yet contexts where the nervous system inhibits tumor growth are less defined. Here, we performed optical reconstruction of axonal innervation in mouse models of cutaneous melanoma, revealing progressive innervation by sympathetic axons. Local depletion of these axons accelerates while local optogenetic activation slows melanoma growth, together consistent with these axons acting as a physiological growth brake. The sympathetic nervous system is typically associated with driving tumor growth through activation of β-adrenergic receptors (ARs). Here, we find that the initial tumor seeding conditions sensitize melanomas from βAR-driven growth promotion toward α2-AR-driven growth inhibition. Mechanistically, the axonal activation of α2 ARs restricts the number and distribution of pro-tumor myeloid cells, independently of T cell activity. Together, our data reveal context-dependent, bidirectional neural control of tumor progression.

Keywords:  Adra2a; adrenergic; cancer neuroscience; iDISCO; innervation; melanoma; neuro-immune; nociceptor; pro-tumor macrophage; sympathetic axon

DOI:  https://doi.org/10.1016/j.neuron.2026.04.016
Abdom Radiol (NY). 2026 Apr 25.

Preoperative prediction of perineural invasion in pancreatic ductal adenocarcinoma using dual-layer spectral CT.

Jiawei Liu, Luyong Wei, Jiadan Luo, Jinhui Yu, Tingting Wen, Weiwei Deng, Shi-Ting Feng, Mingjie Chen, Siya Shi, Yanji Luo.

   PURPOSE: Perineural invasion (PNI) is an independent predictive factor for pancreatic ductal adenocarcinoma (PDAC); however, preoperative prediction is difficult. This study aimed to evaluate the value of dual-layer spectral CT (DLCT) parameters in PNI in PDAC.
MATERIALS AND METHODS: This retrospective study included patients with pathologically confirmed PDAC who underwent DLCT between August 2019 and March 2024. Risk factors were identified using univariable and least absolute shrinkage and selection operator (LASSO) regression. Receiver operating characteristic (ROC), precision-recall (PR) curves, calibration curves and decision curve analysis (DCA) accessed diagnostic performance.
RESULTS: We included 100 patients (mean age: 60.88 ± 11.39 years old, 59 males). There were 71 patients with PNI and 29 without PNI. Relevant factors for PNI included tumour diameter, normalised CT attenuation during the pancreatic parenchymal phase in conventional CT (nCTa), normalised CT attenuation during the pancreatic parenchymal phase in DLCT at 40 keV, and normalised iodine concentration during the pancreatic parenchymal phase (nDIa) (odds ratio [OR], 1.34; 95% confidence interval [CI]: 1.19, 1.51; p < 0.001). Of these, nDIa was the only independent predictor (p < 0.001; adjusted OR, 1.41; 95% CI: 1.19, 1.68) and demonstrated superior diagnostic performance compared to nCTa, with a cutoff value of 0.16, higher area under the curve (ROC: 0.86 vs. 0.68, PR: 0.93 vs. 0.84; both p < 0.001), higher accuracy (77.0% vs. 52.0%, p = 0.048), an F1 score of 0.90, higher sensitivity (71.8% vs. 36.6%, p = 0.03), and the same specificity of 89.7% (p = 0.13). The calibration plot illustrated satisfactory agreement of nDla and DCA confirmed its promising clinical application value.
CONCLUSION: The DLCT parameter nDIa allows for non-invasive prediction of PNI in PDAC with superior diagnostic efficacy compared to conventional CT parameters.

Keywords:  Dual-layer spectral CT; Pancreatic ductal adenocarcinoma; Perineural invasion

DOI:  https://doi.org/10.1007/s00261-026-05529-7
Eur J Surg Oncol. 2026 Apr 17. pii: S0748-7983(26)00430-0. [Epub ahead of print]52(6): 111811

Prognostic significance of perineural invasion in esophageal squamous cell carcinoma: A large-scale propensity score matching analysis with long-term follow-up outcomes.

Zhaoyang Yan, Tongxin Xu, Juntao Lu, Xiaoxu Li, Xinhao Wang, Zhaokun Hu, Wei Guo.

   BACKGROUND: The prognostic significance of perineural invasion (PNI) in esophageal squamous cell carcinoma (ESCC) remains controversial. This study evaluated the impact of PNI on long-term survival in a large surgical cohort.
METHODS: A total of 1211 consecutive patients who underwent esophagectomy with two-field lymphadenectomy for pT1-4aN0-3M0 ESCC at the Fourth Hospital of Hebei Medical University between January 2015 and December 2020 were retrospectively enrolled. PNI status was assessed by both hematoxylin and eosin staining and S100 immunohistochemistry. Propensity score matching (PSM) was employed to balance baseline clinicopathological characteristics. Logistic regression analysis was used to identify factors associated with PNI, and Cox proportional hazards models were applied to evaluate its prognostic significance. Survival outcomes were estimated using the Kaplan-Meier method and compared by log-rank test.
RESULTS: PNI occurred in 23.7% of patients and was independently associated with lymphovascular invasion and advanced T stage. After PSM, 512 patients (256 per group) were included in the survival analysis. Median overall survival was significantly shorter in the PNI-positive group (29.3 months vs. 40.4 months; P < 0.05). Multivariate Cox regression confirmed PNI as an independent predictor of poorer survival (HR 1.24, 95% CI 1.01-1.53; P < 0.05). Subgroup analysis suggested that the prognostic effect of PNI was more pronounced in patients with T3-4 tumors.
CONCLUSION: PNI is an independent adverse prognostic factor for long-term survival in patients with surgically resected ESCC. Routine PNI assessment may refine risk stratification and guide clinical decision-making.

Keywords:  Esophageal squamous cell carcinoma; Perineural invasion; Prognosis; Propensity score matching

DOI:  https://doi.org/10.1016/j.ejso.2026.111811
BMC Med. 2026 Apr 30.

The neuroimmune axis in breast cancer: from mechanistic insights to clinical applications.

Yimao Wu, Kaiyu Zhang, Xinya Xia, Tianqi Zhang, Naijun Jiang, Yu Zhang, Fangqi Zheng, Yuhan Jiang, Xiaorui Xiang, Huijie Miao, Hailin Tang, Shuai Ren, Meng-Yao Li.

   BACKGROUND: Breast cancer is the most commonly diagnosed malignancy in women worldwide, and its marked heterogeneity together with the complexity of the tumor microenvironment contributes to substantial variability in therapeutic responses. Although conventional studies have mainly focused on tumor cell-intrinsic alterations, increasing evidence has identified the neuroimmune axis as a critical regulator of breast cancer progression and treatment resistance.
MAIN BODY: The neuroimmune axis involves bidirectional crosstalk between the nervous system and the immune system, mediated by neurotransmitters, neuropeptides, and neurotrophins. These mediators modulate immune cell activity and reshape tumor behaviors, including proliferation, epithelial-mesenchymal transition, angiogenesis, and metastasis, while immune-derived cytokines can in turn remodel neural circuits and sustain a pro-tumor microenvironment. In this review, we summarize the major mechanisms underlying neuroimmune regulation in breast cancer and discuss emerging therapeutic strategies, including repurposing of neuroactive agents, breast-targeted drug delivery systems, neural stimulation combined with immune checkpoint blockade, and microbiota-neuroimmune interventions. We also outline key challenges to clinical translation, such as the spatiotemporal heterogeneity of neuroimmune regulation, the narrow therapeutic window of neuropharmacological agents, and the lack of standardized biomarkers.
CONCLUSION: A deeper understanding of the neuroimmune axis may provide a theoretical basis for precision therapeutic strategies and help improve outcomes, particularly in therapy-resistant subtypes such as triple-negative breast cancer.

Keywords:  Breast cancer; Immunotherapy; Neuroimmune axis; Neurotransmitters; Neurotrophins; Tumor microenvironment

DOI:  https://doi.org/10.1186/s12916-026-04870-4
Cells. 2026 Apr 21. pii: 735. [Epub ahead of print]15(8):

Neuroglial-Breast Cancer Crosstalk Shapes the Brain Metastatic Niche.

Sabine Hombach-Klonisch, Eric Hall, Reem Amin, Emily Fedora, Jerry Vriend, Marshall Pitz, Thomas Klonisch.

  Breast cancer brain metastasis (BCBM) affects up to 30% of patients with metastatic disease and carries a median survival of only 4-18 months. Emerging evidence reveals that BCBM cells are not passive survivors, but active participants that hijack core neurotransmitter networks, GABA (gamma-aminobutyric acid) and glutamate, to fuel their growth. BCBM, particularly triple-negative breast cancer (TNBC), frequently switch to a GABAergic mode utilizing brain-derived GABA as an oncometabolite. In parallel, BCBM cells can also form direct synapses with neurons, tapping into excitatory input through glutamatergic receptors to drive tumor cell proliferation and survival. Concurrently, reprogrammed astrocytes establish gap junctions, secrete growth factors, and provide metabolic support. Together, tumor cells, neurons, and astrocytes form a pathological partnership locked in feedback loops sustaining metastatic progression. This review focuses on the unique mechanisms employed by distinct breast cancer subtypes and maps the metastatic progression from pre-metastatic to mature brain metastatic niche formation of BCBM. We highlight opportunities to repurpose neurological drugs to disrupt these communication axes.

Keywords:  AMPAR; GABA shunt; GABAergic; HER2+ breast cancer; NMDAR; breast cancer brain metastasis (BCBM); cytonemes; glutamatergic; neuronal mimicry; tripartite synapse; triple negative breast cancer (TNBC); tumor microtubes (TMs); tunneling nanotubes (TNTs); voltage-gated calcium channels (VGCCs)

DOI:  https://doi.org/10.3390/cells15080735
Cell Death Dis. 2026 Apr 25.

Single-cell profiling reveals distinct populations of tumor-associated macrophages and metastatic tumor cells in breast cancer brain metastasis.

Haoyuan Shi, Jiaxin Chen, Zisheng Wu, Dong-Xu Liu, Jinmei Zhou, Xuexue Wu, Ailing Yang, Shanhu Li, Yanhong Tai, Zefei Jiang, Zhiyuan Hu, Mingshan Zhang, Xiaojie Xu, Lu Pan, Tao Wang.

Breast cancer brain metastasis (BCBM) is a major cause of breast cancer-related mortality, but the molecular mechanisms underlying its progression remain poorly understood. Here, we profiled the tumor immune microenvironment of BCBM at single-cell resolution and identified candidate regulators associated with brain metastatic progression. Single-cell RNA sequencing (scRNA-seq) was performed on brain metastatic tissue, adjacent tumor tissue, cerebrospinal fluid, and circulating tumor cells (CTCs) from seven patients, and bulk DNA sequencing was conducted on primary breast tumors, peripheral blood, and brain metastases from 47 patients. Analysis of 131,880 single cells identified 63 distinct cell clusters, including 12 tumor-associated macrophage (TAM) subtypes and 5 metastatic tumor cell (MTC) subtypes. Circulating TAMs displayed an M1-like inflammatory phenotype, whereas tissue-resident TAMs were predominantly M2-like. MTCs exhibited substantial transcriptional heterogeneity, and a neuro-related subtype showed adaptive upregulation of neuronal signaling pathways. Brain metastases also harbored a higher mutational burden than primary tumors, with recurrent mutations in GABRB3 and NRXN1 associated with poorer patient survival. Functional experiments further showed that loss of GABRB3 or NRXN1 impaired tumor growth and brain colonization in xenograft models. These findings nominate GABRB3 and NRXN1 as candidate regulators of brain metastatic fitness in BCBM and support their further evaluation as biomarkers and therapeutic targets.

DOI: https://doi.org/10.1038/s41419-026-08807-w