bims-netuvo 2026-03-29 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–03–29
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.
A cancer neuroscience-related gene model for prognosis prediction and immunotherapy response evaluation in breast cancer.
When stress signals to skin: Sympathetic nerves tune immune surveillance.
Perineural Invasion in Early-Stage Cervical Cancer: Marker of Aggressive Pathology and Increased Recurrence Risk.
Dual-layer detector spectral CT-derived extracellular volume fraction combined with clinical parameters for predicting lymphovascular and perineural invasion in gastric cancer.
Perineural spread of colorectal carcinoma into the sciatic nerve with positive circulating tumor DNA test: illustrative case.
Perineural invasion and risk of lymph node metastasis in early-stage operable breast cancer: a large-scale propensity-matched cohort study and meta-analysis.
Posterior Interosseous Nerve Schwannoma Presenting as a Painless Forearm Mass: A Case Report.
Malignant peripheral nerve sheath tumors arising in SMARCB1-associated schwannomatosis: illustrative cases.
Impact of beta-blockers on prognostic outcomes in solid cancers: a systematic review and meta-analysis.
Relationship Between Gut Microbiota and Cancer Neuro-Immunity.

Front Cell Dev Biol. 2026 ;14 1667459

The neural niche in cancer: mechanistic insights into tumor-neuron-immune crosstalk and therapeutic opportunities.

Nese Aysit, Esra Altintas, Fulya Koksalar Alkan, Gurkan Ozturk, Hasan Korkaya.

  The nervous system is increasingly recognized as a dynamic and regulatory component of the tumor microenvironment playing critical roles in cancer initiation, progression, metastasis, and resistance to therapy. Recent evidence in cancer neuroscience have revealed a specialized "neural niche" a microanatomical and functional domain enriched in neural inputs and neuromodulatory signals orchestrated through bidirectional communication between tumor, nervus system and immune cellsCancer cells secrete neurotrophic factors such as nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell line-derived neurotrophic factor (GDNF) to attract and remodel peripheral innervation. Infiltrating nerve fibers, in turn, release neurotransmitters (e.g., norepinephrine, acetylcholine) and neuropeptides (e.g., substance P, calcitonin gene-related peptide) that influence not only tumor growth, angiogenesis but also immune cell polarization, T cell exhaustion, dendritic cell maturation and myeloid derived suppressor cell recruitment. This neural-immune crosstalk establishes immune suppressive microenvironment that facilitates tumor immune escape and leading to metastatic progression. Perineural invasion (PNI), a distinct pathological process of tumor dissemination, further exemplifies neuroepithelial integration and correlates with recurrence, pain and poor prognosis across multiple solid tumors. Beyond local interactions, chronic stress and systemic neuroendocrine activation via the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic-adrenal-medullary networks, contribute to tumor-promoting immunosuppression through glucocorticoid signaling and sympathetic responses. In this review, we discuss mechanistically integrated and clinical relevant synthesis of tumor-neuron-immune interactions. We emphasize recent conceptual advances, including autonomic balance, systemic neuroendocrine feedback and therapeutic strategies targeting this axis. These insights establish a framework for future translational research and development of neuromodulatory therapies that complement immunotherapy as well as conventional therapeutics.

Keywords:  adrenergic signaling; cancer-neuron-immune axis; neurotransmitters; neurotrophic factors; perineural invasion; tumor innervation; tumor microenvironment

DOI:  https://doi.org/10.3389/fcell.2026.1667459
Discov Oncol. 2026 Mar 22.

A cancer neuroscience-related gene model for prognosis prediction and immunotherapy response evaluation in breast cancer.

Yansha Wei, Jiehua Li, Mengyang Li, Caixin Qiu.

   BACKGROUND: Breast cancer prognosis remains challenging, and the emerging field of cancer neuroscience suggests that the nervous system plays a crucial yet underexplored role in tumor progression. This study aimed to construct and validate a novel prognostic signature for breast cancer based on genes involved in neural-tumor interactions.
METHODS: Differential expression analysis and univariate Cox regression were performed on the TCGA-BRCA dataset to identify genes associated with both cancer neuroscience and patient prognosis. A prognostic model was constructed using LASSO and multivariate Cox regression analyses. Its predictive performance was validated in external datasets. The immune microenvironment, tumor mutation burden, and immunotherapy response were compared between the high- and low-risk groups. Drug sensitivity was predicted using the oncoPredict algorithm.
RESULTS: A 12-gene prognostic model was developed. Patients stratified into high- and low-risk groups showed significant survival differences in all cohorts. The signature demonstrated reliable predictive accuracy, with AUCs of 0.700, 0.744, and 0.759 for 1-, 3-, and 5-year survival in the TCGA dataset. The low-risk group exhibited a more immunologically active tumor microenvironment,suggesting a potentially better response to immunotherapy. Drug sensitivity analysis identified three compounds with lower predicted IC50 values in the high-risk group.
CONCLUSION: This study establishes and validates a novel 12-gene cancer neuroscience-related prognostic model for breast cancer. This model not only effectively stratifies patient risk but also reveals distinct immune landscapes and predicts differential responses to immunotherapy and potential therapeutic agents. These findings offer new insights for prognostication and personalized treatment strategies in breast cancer.

Keywords:  Breast cancer; Cancer neuroscience; Prognostic model

DOI:  https://doi.org/10.1007/s12672-026-04906-4
Dev Cell. 2026 Mar 23. pii: S1534-5807(26)00118-8. [Epub ahead of print]

When stress signals to skin: Sympathetic nerves tune immune surveillance.

Grecia Ortiz Flores, Sakeen Wali Kashem.

Neural signals are increasingly recognized as modulators of cancer immunity, yet how they influence immune memory within tissues remains unclear. Zhang et al. reveal that sympathetic signaling acts indirectly through epidermal keratinocytes to restrain tissue-resident memory T cell positioning in the skin, uncovering a neuro-epithelial mechanism that shapes tumor immunosurveillance.

DOI: https://doi.org/10.1016/j.devcel.2026.03.006
Biomedicines. 2026 Mar 05. pii: 591. [Epub ahead of print]14(3):

Perineural Invasion in Early-Stage Cervical Cancer: Marker of Aggressive Pathology and Increased Recurrence Risk.

Lihua Tan, Hongyao Li, Tianyi Liu, Wei Mao, Yan Song, Dan Zhao.

  Background: Perineural invasion (PNI) is associated with aggressive tumor behavior in several malignancies, but its independent prognostic value in early-stage cervical cancer remains uncertain. We evaluated the clinical significance of PNI and explored molecular and immune features associated with PNI. Methods: We retrospectively analyzed 499 patients with FIGO 2009 stage IB-IIA cervical cancer treated with radical hysterectomy and pelvic lymphadenectomy. Associations between PNI, clinicopathological variables, recurrence-free survival, and overall survival were assessed using Kaplan-Meier methods and Cox regression. An independent cohort of 286 cervical cancers from The Cancer Genome Atlas (TCGA) was analyzed to characterize PNI-associated transcriptomic patterns, pathway enrichment, immune cell composition, and microRNA profiles. Results: PNI was identified in 11.6% of cases and was associated with larger tumor size, deep stromal invasion, and lymphovascular space invasion. PNI was not an independent prognostic factor in the overall cohort; however, it was associated with increased recurrence risk in the subgroup without high-risk factors and not meeting Sedlis criteria, with a modest improvement in 5-year recurrence discrimination when incorporated into Sedlis-based models. In TCGA, PNI was associated with differential gene expression and enrichment of oncogenic and immune-related pathways, an increased estimated abundance of resting mast cells, and six differentially expressed microRNAs. Conclusions: In early-stage cervical cancer, PNI is strongly correlated with established adverse pathological features and shows a subgroup-specific association with recurrence in an otherwise low-risk postoperative population. The multi-omics findings are exploratory and support biological hypotheses regarding tumor-nerve-immune interactions; external validation is needed before PNI can be used to guide postoperative management.

Keywords:  TCGA; cervical cancer; early stage; immune microenvironment; microRNA; perineural invasion; prognosis; recurrence; risk stratification; transcriptomics

DOI:  https://doi.org/10.3390/biomedicines14030591
Abdom Radiol (NY). 2026 Mar 27.

Dual-layer detector spectral CT-derived extracellular volume fraction combined with clinical parameters for predicting lymphovascular and perineural invasion in gastric cancer.

Rui Guo, Ke Chang, QingHong Yan, Xinyue Xu, Peng Ma, YunHang Jing.

   OBJECTIVE: This study aimed to evaluate the feasibility and diagnostic performance of extracellular volume fraction (ECV), derived from iodine concentration (IC) values obtained through dual-layer detector spectral CT, in combination with clinical parameters, for preoperative prediction of lymphovascular invasion and/or perineural invasion (LVI/PNI) in gastric cancer.
METHODS: This retrospective study included clinical and pathologic data of 124 patients diagnosed with GC at our hospital between September 2023 and February 2025. The patients were stratified into LVI/PNI-positive (n = 85) and LVI/PNI-negative (n = 39) groups based on their postoperative histopathologic findings. All patients underwent contrast-enhanced dual-layer detector spectral CT. Preoperative hematocrit levels were obtained, and IC values within the tumor were measured during the delayed phase. Concurrently, IC in the abdominal aorta at the same anatomical level was measured to calculate the ECV using the formula: ECV = (1 - hematocrit) × (IC_tumor / IC_blood). Clinical variables and spectral CT parameters were analyzed using univariate analysis, LASSO selection, and multivariable logistic regression to identify independent predictors of the composite LVI/PNI endpoint. The diagnostic performance of individual parameters and the combined model for preoperatively predicting vascular and neural invasion was assessed using receiver operating characteristic (ROC) curve analysis.
RESULTS: ECV, CT-N stage, and Borrmann classification were identified as independent predictors of the composite LVI/PNI endpoint in patients with GC (all P < 0.05). Among the candidate models, the combined model incorporating ECV, CT-N stage, and Borrmann classification achieved the best predictive performance, with AUCs of 0.920 in the training cohort and 0.917 in the validation cohort. DeLong analysis showed that the combined model significantly outperformed the CT-N stage model and the Borrmann classification model in both cohorts. However, its improvement over the ECV-only model was not statistically significant.
CONCLUSIONS: Delayed-phase dual-layer detector spectral CT-derived ECV is a promising noninvasive biomarker for identifying the composite LVI/PNI endpoint in gastric cancer. A combined model integrating ECV, CT-N stage, and Borrmann classification provides the best overall diagnostic performance, although its incremental benefit over ECV alone appears limited.

Keywords:  Dual-layer detector spectral CT; ECV; Extracellular volume fraction; Gastric cancer; LVI; Lymphovascular invasion; PNI; Perineural invasion

DOI:  https://doi.org/10.1007/s00261-026-05475-4
J Neurosurg Case Lessons. 2026 Mar 23. pii: CASE25997. [Epub ahead of print]11(12):

Perineural spread of colorectal carcinoma into the sciatic nerve with positive circulating tumor DNA test: illustrative case.

Pavlos Texakalidis, Cara C Prideaux, P James B Dyck, Hao Xie, Robert J Spinner.

   BACKGROUND: Perineural spread (PNS) of colorectal carcinoma (CRC) is a rare and challenging diagnosis. Its clinical and radiological presentation is often subtle and can overlap with radiation-induced neuropathy and malignant nerve tumors, complicating timely diagnosis. The role of circulating tumor DNA (ctDNA) in the detection of PNS has not been previously described.
OBSERVATIONS: A 48-year-old man with a history of rectal cancer and perineural invasion presented with progressive, refractory sciatic neuropathic pain. Conventional surveillance imaging was initially negative despite subtle rising of carcinoembryonic antigen and ctDNA levels. Subsequent MRI revealed abnormalities of the lumbosacral plexus and sciatic nerve, and fascicular biopsy confirmed metastatic CRC involving the sciatic nerve, establishing the diagnosis of PNS.
LESSONS: This case highlights PNS as a rare but important consideration in patients with focal neuropathic symptoms and prior CRC. Circulating tumor DNA positivity may serve as an early indicator of occult tumor activity even within the nerves when imaging is equivocal. However, currently histopathological confirmation remains the only definitive method to distinguish PNS from alternative diagnoses and is essential to guide appropriate management. https://thejns.org/doi/10.3171/CASE25997.

Keywords:  colorectal cancer; ctDNA; perineural invasion; perineural spread

DOI:  https://doi.org/10.3171/CASE25997
Ther Adv Med Oncol. 2026 ;18 17588359261424685

Perineural invasion and risk of lymph node metastasis in early-stage operable breast cancer: a large-scale propensity-matched cohort study and meta-analysis.

Weifeng Cai, Yali Wang, Yibin Qiu, Peng He, Qindong Cai, Shunyi Liu, Jiaqi Zhan, Minyan Chen, Lili Chen, Chunsen Xu, Shunguo Lin, Fangmeng Fu, Chuan Wang.

   Background: Perineural invasion (PNI) is recognized as a prognostic factor in several cancers, but its role in predicting axillary lymph node metastasis (ALNM) in early-stage breast cancer remains unclear. Understanding this association could provide insights for nodal staging in the era of axillary surgery de-escalation, guiding adjuvant treatment decisions.
Objectives: To investigate and validate the association between PNI and both the presence and extent of ALNM in patients with early-stage operable invasive breast cancer.
Design: A retrospective cohort study and meta-analysis.
Methods: We conducted a retrospective study of patients with early-stage operable breast cancer who underwent surgery between June 2011 and June 2023 stratified by PNI status. Three matching methods-propensity score matching, inverse probability of treatment weighting, and overlap weighting-were used to minimize confounding. Multivariable logistic regression analysis was used to assess the association between PNI and both ALNM and lymph node ratio (LNR). In addition, a meta-analysis was conducted to verify these associations.
Results: Among 4156 patients, 1223 (29.4%) were PNI-positive. PNI-positive patients had a significantly higher incidence of ALNM (54.0% vs 32.1%) and increased lymph node burden (LNR >0.20). These associations remained significant after adjusting for confounding variables and through sensitivity analyses using the three matching methods (all p < 0.05). In the meta-analysis, 16 cohort studies comprising 17,451 participants met the selection criteria. The analysis confirmed a significant association between PNI and increased ALNM risk (odds ratio (OR), 3.30; 95% confidence interval (CI), 2.24-4.86), poorer disease-free survival (hazard ratio (HR), 1.84; 95% CI, 1.39-2.44), and poorer overall survival (HR, 1.64; 95% CI, 1.15-2.35).
Conclusion: PNI is significantly associated with increased ALNM and lymph node burden in early-stage operable breast cancer. These findings support the clinical utility of PNI for risk stratification and as a potential indicator for guiding adjuvant treatment decisions.

Keywords:  axillary lymph node metastasis; breast cancer; meta-analysis; perineural invasion; propensity score

DOI:  https://doi.org/10.1177/17588359261424685
Cureus. 2026 Feb;18(2): e103815

Posterior Interosseous Nerve Schwannoma Presenting as a Painless Forearm Mass: A Case Report.

Radhika G Nair, Manal M Khan, Ved Prakash Rao Cheruvu, Prateek Jain, Arun A J.

  Schwannomas are benign peripheral nerve sheath tumors that typically exhibit slow growth and may present diagnostic challenges when arising from uncommon sites. We report the case of a 65-year-old female who presented with a six-year history of a gradually enlarging, painless swelling over the extensor aspect of the left forearm. The lesion initially appeared as a small nodule and progressively enlarged to approximately 4 × 3 cm, with intermittent tingling and occasional numbness but no significant functional impairment. Clinical examination revealed a firm, well-defined mass with a positive Tinel's sign. Ultrasonography and contrast-enhanced MRI demonstrated a well-circumscribed, encapsulated lesion along the course of the posterior interosseous nerve (PIN) in the intermuscular plane, suggestive of a benign peripheral nerve sheath tumor. The patient underwent planned microsurgical excision under general anesthesia. Intraoperatively, the tumor was found to arise eccentrically from the PIN and was meticulously dissected from the surrounding nerve fascicles, allowing complete excision while preserving nerve continuity. Histopathological examination confirmed the diagnosis of schwannoma, demonstrating characteristic Antoni A and Antoni B areas, Verocay bodies, and thick-walled hyalinized vessels. The postoperative course was uneventful, with preservation of motor and sensory function and no evidence of recurrence on follow-up. This report underscores the importance of thorough clinical evaluation and appropriate imaging in the diagnosis of peripheral nerve tumors of the forearm and highlights the role of meticulous microsurgical technique in achieving complete tumor excision with excellent functional outcomes.

Keywords:  antoni a areas; antoni b areas; peripheral nerve tumor; posterior interosseous nerve; schwannoma; tinels sign; verocay bodies

DOI:  https://doi.org/10.7759/cureus.103815
J Neurosurg Case Lessons. 2026 Mar 16. pii: CASE25610. [Epub ahead of print]11(11):

Malignant peripheral nerve sheath tumors arising in SMARCB1-associated schwannomatosis: illustrative cases.

Taha Khalilullah, Xinlan Yang, Jonathan Yao, Abdul Karim Ghaith, Jawad M Khalifeh, Tej D Azad, A Karim Ahmed, Yuanxuan Xia, Nicholas Theodore, Carlos G Romo, Jean-Paul Wolinsky, Allan J Belzberg, Daniel Lubelski.

   BACKGROUND: Schwannomatosis is a rare tumor predisposition syndrome characterized by benign peripheral nerve sheath tumors in the absence of bilateral vestibular schwannomas. In rare cases, malignant peripheral nerve sheath tumors (MPNSTs) may arise with schwannomatosis, particularly with SMARCB1 mutations. These malignancies pose significant diagnostic and therapeutic challenges and a poor prognosis.
OBSERVATIONS: The authors present 2 cases of high-grade MPNST with SMARCB1-associated schwannomatosis. Both presented with rapidly enlarging and concerning imaging features, including heterogeneous enhancement, central necrosis, and low apparent diffusion coefficient values. Histopathological analysis confirmed high-grade MPNST with elevated mitotic activity and loss of H3K27me3. Both patients underwent en bloc resection with negative margins. One patient remains disease free at 5 years; the other patient developed metastatic recurrence and died. A systematic review identified 20 cases in the literature.
LESSONS: These cases emphasize clinical vigilance for malignant transformation in schwannomatosis, particularly with rapidly enlarging lesions or new neurological symptoms. MRI and FDG-PET can aid in identifying concerning features. Despite margin-negative resection, recurrence and metastasis may occur, reflecting the tumor's aggressive biology. Genetic counseling may be considered in SMARCB1-associated cases. While malignant transformation is much more common in NF1 lesions, rare cases do arise in schwannomatosis, requiring close surveillance and multidisciplinary management. https://thejns.org/doi/10.3171/CASE25610.

Keywords:  MPNST; SMARCB1; illustrative case; schwannomatosis

DOI:  https://doi.org/10.3171/CASE25610
J Natl Cancer Inst. 2026 Mar 21. pii: djag082. [Epub ahead of print]

Impact of beta-blockers on prognostic outcomes in solid cancers: a systematic review and meta-analysis.

Sule Eraslan, Emine Ceren Ayhan, Michael Tvilling Madsen, Erica K Sloan, Ismail Gögenur, Adile Orhan.

BACKGROUND: Beta-blockers are conventionally prescribed for cardiovascular indications and have potential for repurposing in oncology as adrenergic signalling promotes cancer progression. This systematic review and meta-analysis evaluated whether beta-blocker use is associated with improved survival outcomes in patients with all stages of solid cancer.
METHODS: This systematic review and meta-analysis was conducted in accordance with PRISMA guidelines using a predefined (PICO) framework. Four databases (PubMed, Embase, Cochrane Library, and Web of Science) were searched. Eligible studies compared beta-blocker users with non-users and reported survival outcomes in patients with solid cancer. Outcomes included overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), progression-free survival (PFS) and recurrence-free survival (RFS). Risk of bias was assessed using the Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias 2 tool. Certainty of evidence was evaluated using GRADE.
RESULTS: A total of 5122 articles were screened; 94 articles were included in the systematic review and 84 in the meta-analysis comprising 603,827 patients. Beta-blocker use in patients with solid cancers was associated with significantly improved OS (HR 0.88, 95% CI: 0.80-0.96) and PFS (HR 0.82, 95%CI: 0.69-0.97). The greatest effects on OS were observed in patients with gastrointestinal (HR 0.84, 95%CI: 0.72-0.98), lung (HR 0.84, 95%CI: 0.71-0.99), and skin cancers (HR 0.81, 95%CI: 0.73-0.89). Effects appeared stronger with post-diagnostic exposure and in certain cancer subtypes, however, heterogeneity and the observational nature of most included studies warrant cautious interpretation.
CONCLUSION: Beta-blocker use was associated with improved OS and PFS in patients with solid cancers.

DOI: https://doi.org/10.1093/jnci/djag082
Microb Biotechnol. 2026 Mar;19(3): e70336

Relationship Between Gut Microbiota and Cancer Neuro-Immunity.

Danyang Wang, Ruirui Cui, Chang You, Wanlin Zheng, Luyao Wang, Yingqi Yang, Hongkai Yu, Bota Cui.

  The nervous system and the immune system are integral components of the tumour microenvironment, and neuroimmune mechanisms play critical roles in tumour metastasis, immune evasion and metabolic reprogramming. However, the relationship between the gut microbiota and cancer neuro-immunity remains poorly understood. This knowledge gap hampers our understanding of how these systems contribute to tumour progression and therapeutic resistance. This article systematically explores the interactions among the gut microbiota, the nervous system and the immune system in the regulation of tumour progression, with a particular focus on elucidating the pathways by which the gut microbiota and its metabolites modulate tumour phenotypes via neuroimmune mechanisms, and summarises the regulatory mechanisms through which cancer neuro-immunity shapes gut microbiota composition. Additionally, this article summarises the interplay between immunotherapy and cancer neuro-immunity, and explores the potential of microbiota-based interventions, such as faecal microbiota transplantation, probiotics, prebiotics and synbiotics, to enhance the efficacy of immunotherapy through neuroimmune mechanisms.

Keywords:  gut microbiota; immunotherapy; neuroimmunity; tumour microenvironment

DOI:  https://doi.org/10.1111/1751-7915.70336