bims-netuvo 2026-03-08 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–03–08
nine papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine.
The crosstalk between nerves and immunity: chronic stress as a driver of tumor progression.
Nociceptive neuroimmune circuit drives immune evasion.
Lost rhythms: Breast cancer hijacks neuronal circuits that blunt GC rhythms to promote tumor progression.
Neuroimmunometabolic co-evolution in the tumor micro- and macroenvironment.
Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors.
IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.
Schwannoma: a spectrum from benign to malignant.
Single-cell advances in the investigation of the pathogenesis and treatment of brain metastasis.

Gen Hosp Psychiatry. 2026 Feb 25. pii: S0163-8343(26)00038-1. [Epub ahead of print]100 1-11

Advancing cancer neuroscience through stress modulation: Interdisciplinary potential of psilocybin and ketamine.

Alan C Courtes, Blake Myers, Noah Daly, Greg Jones, Jair C Soares, Carlos A Zarate, Rodrigo Machado-Vieira.

  Psychological stress not only undermines quality of life for people with cancer but also fuels tumor growth. Emerging evidence from the nascent field of cancer neuroscience suggests that adrenergic signaling from direct tumor-neuron interactions drives cancer progression, resistance to treatment, and worse outcomes. Cancer neuroscientists are increasingly seeking to repurpose psychoactive medications (e.g., β-blockers and others) to augment primary cancer therapies. Preclinical models reveal that psychological stress can be a key activator of the sympathetic pathways that promote pathological tumor-neuron crosstalk. However, conventional antidepressants/anxiolytics used to address psychological distress are often less effective in this population. Conversely, while sample sizes are limited, psilocybin has achieved 60-80% long-term remission of cancer-related depression and anxiety and peri-palliative ketamine studies demonstrate rapid but short-lived symptom control. In preclinical models these agents appear to normalize hypothalamic-pituitary-adrenal (HPA) axis function while upregulating neurotrophic factors, mechanisms which putatively promote stress reductions and resilience. In this review, we propose that this neuroplastic recalibration may reduce sustained adrenergic tone, thereby interrupting the stress-driven tumor-neuron signaling that accelerates cancer progression. Integrating these rapid agents into oncology practice could thus disrupt maladaptive adrenergic signaling, enhance treatment adherence, and ultimately improve survival. Hospital-based psychiatrists are uniquely positioned to lead this effort by collaborating with oncologists, embedding biomarker-rich clinical trials, and monitoring both psychiatric and tumor-neuron interaction metrics. Advancing interdisciplinary research with ketamine and psilocybin will clarify whether targeting systemic stress indices represents a cancer-relevant endpoint beyond psychological symptom relief itself, while advancing research in cancer neuroscience mechanisms to improve oncologic outcomes.

Keywords:  Adrenergic signaling; Cancer neuroscience; Ketamine; Psilocybin; Stress

DOI:  https://doi.org/10.1016/j.genhosppsych.2026.02.011
Front Immunol. 2026 ;17 1758894

The crosstalk between nerves and immunity: chronic stress as a driver of tumor progression.

Yuan He, Haoliang Yu, Fengze Li, Junzhe Liu, Zhihao Chen, Wenping Zhu, Li Yang, Tengfeng Yan.

  Chronic stress, a sustained psychophysiological state, promotes tumor progression primarily by disrupting anti-tumor immunity. Through persistent activation of the HPA axis and sympathetic nervous system, stress hormones such as glucocorticoids and catecholamines reshape the tumor microenvironment and systemically impair immune surveillance. This leads to suppressed activity of cytotoxic lymphocytes, expansion of immunosuppressive cells, and ultimately, enhanced immune evasion and metastasis. Furthermore, these pathways undermine the efficacy of conventional and emerging therapies by fostering multidrug resistance. This review highlights these mechanisms and discusses the promise of targeting stress signaling, through both pharmacological and behavioral interventions, as a strategy to improve cancer outcomes. To address the current lack of clinical guidelines for counteracting the cancer progression mediated by chronic stress, this review propose a tiered screening and intervention model based on easily accessible biostress biomarkers. This hypothesis aims to bridge the gap between basic mechanism research and clinical application, providing a theoretical foundation directional guidance for future research.

Keywords:  cancer; catecholamines; chronic stress; glucocorticoids; hypothalamic-pituitary-adrenal axis; stress management; tumor immunity

DOI:  https://doi.org/10.3389/fimmu.2026.1758894
Trends Cancer. 2026 Mar 02. pii: S2405-8033(26)00003-8. [Epub ahead of print]

Nociceptive neuroimmune circuit drives immune evasion.

Canhui Cao.

  Tumor-associated sensory nerves are emerging regulators of cancer immunity, yet their role in systemic immunosuppression remains unclear. Zhang et al. revealed that tumors hijack an interorgan nociceptor-slit guidance ligand 2-calcitonin gene-related peptide circuit to escape immune surveillance. Disrupting this neural loop restores T-cell function and enhances immunotherapy efficacy.

Keywords:  CGRP; cancer immunology; cancer neuroscience; immune evasion; neuron–immune crosstalk; nociceptive neuron

DOI:  https://doi.org/10.1016/j.trecan.2026.01.003
Neuron. 2026 Mar 04. pii: S0896-6273(26)00091-7. [Epub ahead of print]114(5): 789-790

Lost rhythms: Breast cancer hijacks neuronal circuits that blunt GC rhythms to promote tumor progression.

Francesco De Virgiliis, Christoph Scheiermann.

In this issue of Neuron, Gomez et al.1 report that breast cancer disrupts diurnal glucocorticoid oscillations by disinhibiting hypothalamic CRH neurons. Time-specific neuromodulation restores rhythms and attenuates tumor growth by enhancing CD8+ T cell functions. This unveils a mechanism whereby cancer utilizes brain circuits that could be targetable with chronotherapy.

DOI: https://doi.org/10.1016/j.neuron.2026.02.008
Cell Metab. 2026 Feb 27. pii: S1550-4131(26)00044-6. [Epub ahead of print]

Neuroimmunometabolic co-evolution in the tumor micro- and macroenvironment.

Yu Zhang, Weijie Zhuang, Haodong Zhu, Fansheng Meng, Mingtao Chen, Yibo Guo, Jia Fan, Yunfan Sun, Tong Ji.

  The nervous system integrates immune, endocrine, and circulatory systems to coordinate complex physiological responses. It influences tumor progression and treatment resistance through interactions with cancer cells and immune cells and by regulating metabolic processes within both the tumor microenvironment (TME) and tumor macroenvironment (TMaE). This review provides a comprehensive overview of the neuroimmunometabolic co-evolution within the TME and TMaE. At the TME scale, we discuss the role of the peripheral nervous system (PNS), including sympathetic, parasympathetic, and sensory neurons, in regulating metabolic processes and immune cell functions. At the TMaE scale, we highlight how cancer cells exploit brain-body interactions to reprogram systemic metabolism and immune responses, creating conditions that favor tumor progression. Additionally, we describe how the PNS serves as a conduit for long-range communication between tumors and distant organs. Finally, we identify key knowledge gaps, propose strategies to address current limitations, and discuss clinically actionable neuroimmune and neurometabolic therapies.

Keywords:  brain-body interactions; cancer immunology; cancer metabolism; cancer neuroscience; neuroimmune interactions; neurometabolic interactions; tumor macroenvironment; tumor microenvironment

DOI:  https://doi.org/10.1016/j.cmet.2026.02.001
Neurooncol Adv. 2026 Mar;8(Suppl 1): i43-i50

Single-cell transcriptomic profiling of malignant peripheral nerve sheath tumors.

Chloe Gui, Severa Bunda, Mira Li, Olivia Singh, Gelareh Zadeh, Suganth Suppiah.

  Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas arising from Schwann cells and characterized by marked cellular and molecular heterogeneity. Although bulk multi-omic studies have provided valuable insights into MPNST biology, recent advances in single-cell profiling have deepened our understanding of the tumor microenvironment and molecular mechanisms underlying malignant transformation. Single cell analyses have revealed distinct Schwann cell-like, malignant neural crest-like, immune, and stromal cellular subpopulations within MPNSTs and their precursor lesions. Comparative profiling of MPNSTs, neurofibromas, and atypical neurofibromatous neoplasms of uncertain biologic potential, suggest that MPNST progression involves Schwann cell dedifferentiation into a more primitive, stem-like state. In this review, we summarize key discoveries from single-cell characterization studies, and discuss how these findings illuminate MPNST tumorigenesis, cellular plasticity, and potential therapeutic vulnerabilities.

Keywords:  MPNST; malignant peripheral nerve sheath tumor; neurofibroma; neurofibromatosis; single-cell

DOI:  https://doi.org/10.1093/noajnl/vdaf243
J Clin Invest. 2026 Mar 02. pii: e195652. [Epub ahead of print]136(5):

IFN signaling is associated with radiotherapy response in malignant peripheral nerve sheath tumors.

Iowis Zhu, Julian Chien, Gabriel E Rech, Kanish Mirchia, Sixuan Pan, Kaeli Miller, Joanna Pak, Rosanna Wustrack, Varun Monga, Steve E Braunstein, Mark D Adams, Line Jacques, Melike Pekmezci, S John Liu, Harish N Vasudevan.

  Patients with malignant peripheral nerve sheath tumors (MPNSTs) have poor outcomes despite multimodal treatment with surgery, radiation, and systemic therapy. The responses to radiotherapy (RT) are mixed, and the biologic mechanisms underlying this heterogeneity in the radiation response of MPNSTs are not understood. Here, we combined bulk and single-cell transcriptomics, genome-wide CRISPR interference screens, and multiplatform molecular analysis across MPNST cells, mouse allograft models, and patients' samples to understand the mediators of the radiation response. Our data revealed that MPNSTs, but not benign plexiform neurofibromas, induced a type I IFN signature that functionally mediated the radiation response. Moreover, irradiation of immunocompetent mouse MPNST allografts led to IFN-mediated T cell recruitment and activation. Both host mouse T cells and intact tumor IFN receptor signaling were required for RT's efficacy in mouse MPNST allografts. Analysis of human MPNST resection specimens demonstrated that increased microenvironmental and CD8+ T cell infiltration were associated with improved local control following RT. These results provide a preclinical rationale for combining immunomodulatory agents targeting IFN signaling to improve radiation responses in MPNSTs and potentially other soft tissue sarcomas.

Keywords:  Cancer; Cytokines; Genetics; Immunology; Oncology; Radiation therapy

DOI:  https://doi.org/10.1172/JCI195652
Rom J Morphol Embryol. 2025 Oct-Dec;66(4):66(4): 673-681

Schwannoma: a spectrum from benign to malignant.

Andreea Cătălina Tinca, Bianca Andreea Lazăr, Andreea Raluca Cozac-Szőke, Raluca Diana Hagău, Diana Maria Chiorean, Adrian Horaţiu Sabău, Cornelia Titiana Cotoi, Raluca Niculescu, Iuliu Gabriel Cocuz, Jenő Róbert Bartha, Sabin Gligore Turdean, Ovidiu Simion Cotoi.

  Peripheral nerve sheath tumors are a group of neoplasms that arise from Schwann cells. This study evaluates the histopathological and immunohistochemical (IHC) characteristics of these entities, spanning a spectrum from benign to malignant lesions. We focused on tumor variants, particularities, and differential diagnoses. A total of 25 cases were analyzed, with conventional schwannomas being the most common benign tumor subtype. Classic schwannomas exhibited typical Antoni A and Antoni B patterns, with Verocay bodies as defining features. Additionally, less common variants, such as cystic and myxoid schwannomas, were identified, highlighting the morphological variations of these entities. Malignant peripheral nerve sheath tumors (MPNSTs), representing the malignant counterpart, were characterized by spindle cell and epithelioid morphologies, high mitotic activity, and aggressive clinical behavior. Differentiating MPNSTs from other soft tissue tumors, such as neurofibromas and melanomas, was challenging due to overlapping histological features. IHC markers, particularly S100 and sex determining region Y (SRY)-box transcription factor 10 (SOX10), played an important role in the diagnostic process, though their interpretation required precision to avoid diagnostic pitfalls. This study highlights the importance of integrating histopathology and immunohistochemistry for accurate diagnosis and differentiation of peripheral nerve sheath tumors. The recognition of rare variants and analysis of tumor subtypes contribute to a better understanding of these entities, which is crucial for appropriate clinical management.

Keywords:  immunohistochemistry; malignant peripheral nerve sheath tumor; morphology; schwannoma

DOI:  https://doi.org/10.47162/RJME.66.4.05
Neurooncol Adv. 2026 Mar;8(Suppl 1): i17-i28

Single-cell advances in the investigation of the pathogenesis and treatment of brain metastasis.

Robert S Porter, Clara Alves-Pereira, Priscilla K Brastianos.

  Brain metastasis remains a significant cause of morbidity and mortality for cancer patients with limited treatment options. Single-cell RNA-seq has greatly expanded our ability to study cancer and metastasis, particularly in our assessment of tumor heterogeneity and the tumor microenvironment. In recent years, there have been several single-cell studies that have applied this technology to brain metastasis. These studies have described transcriptional characteristics of brain metastatic tumor cells and characterized immune cell changes as well as contributions of vascular and stromal cells to the brain metastatic microenvironment. This review article summarizes these studies, how they contribute to our knowledge of the molecular and cellular steps that occur in brain metastasis and in response to therapy, and how they suggest promise for future treatments.

Keywords:  brain metastasis; organotropism; single-cell sequencing

DOI:  https://doi.org/10.1093/noajnl/vdaf108