bims-netuvo 2026-05-31 papers

bims-netuvo

Biomed News

on Nerves in tumours of visceral organs

Issue of 2026–05–31
eleven papers selected by
Maksym V. Kopanitsa, Charles River Laboratories

Purinergic signaling and cancer neuroscience.
Disrupting neuro-immune feedback loops: novel targets to amplify cancer immunotherapy.
How the connection between lung cancer and the brain could lead to better treatments.
Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic.
An interpretable multimodal model integrating clinical, spectral CT imaging, and deep learning analysis of intra- and peritumoral regions for preoperative prediction of perineural invasion in gastric cancer: A prospective, multicenter study.
The value of extracellular volume based on spectral CT in lymph node metastasis, perineural invasion, and lymphovascular invasion of colon cancer.
Neural state as a determinant of tumor immunity in lung cancer.
Characterizing Pain in Peripheral Nerve Tumors: Interim Results from a Prospective Bicenter Cohort.
Large Malignant Peripheral Nerve Sheath Tumor Arising From the Sciatic Nerve in a Patient With Neurofibromatosis Type 1.
EXPRESS: RIN1 inhibited TRPV1-dependent pain sensitization in a mouse model of bone cancer pain.
Assessment and Management of Cancer-Related Cognitive Impairment.

Neuropharmacology. 2026 May 28. pii: S0028-3908(26)00222-4. [Epub ahead of print] 111048

Purinergic signaling and cancer neuroscience.

Jia-Qi Hu, Xiao-Die Zhou, Qing-Ling Ren, Yue Han.

  The emerging field of cancer neuroscience has revealed that the nervous system plays an important role in tumor initiation, progression, metastasis, and therapeutic resistance. Purinergic signaling has been recognized as a critical regulatory system in neuroscience and cancer, respectively. This review collected current understandings of purinergic signaling in cancer and neuroscience and pointed out that why purinergic signaling could work in cancer neuroscience and how to work in neuroscience. It also proposed that purinergic signaling represents a critical target in cancer neuroscience, offering both mechanistic insights and translational opportunities for the development of next-generation cancer therapeutics, especially P2X7R, CD39/CD73, A2AR, P2X3R will offer unprecedented opportunities to intervene at the neural-tumor interface for the treatment of cancer in the future.

Keywords:  cancer neuroscience; perineural invasion; purinergic signaling; tumor microenvironment

DOI:  https://doi.org/10.1016/j.neuropharm.2026.111048
Immunotherapy. 2026 May 27. 1-28

Disrupting neuro-immune feedback loops: novel targets to amplify cancer immunotherapy.

Abbas Jafari, Kovsar Mohammadnezhadharmileh, Maryam Majidinia, Soheil Vazifedust, Ebrahim Mazloomi.

  Nervous system and immune system have tight interactions that modulate both nerves and immune cells' activities. The interplay between the nervous and immune systems within the tumor microenvironment is a critical yet underexplored determinant of cancer immunotherapy efficacy. This review presents a new model called the Neuro-Immune Feedback Loop, which suggests that two-way communication (like the immunosuppressive effects of norepinephrine and the influence of cytokines on nerve activity) creates self-perpetuating cycles that tumors use to avoid immune responses. We compile evidence regarding neurotransmitters (such as dopamine), neuropeptides (like CGRP) to suggest innovative strategies to disrupt the immune-nerve loops. The current review proposes that context-sensitive neuro-immune switches (for instance, the dual functions of GABA) and multi-target therapies (such as CRISPR-modified neurons combined with immune checkpoint inhibitors (ICIs) could enhance immunotherapy effectiveness. By connecting neuroscience with immunology and oncology, this review aims to provide a roadmap for overcoming resistance to immunotherapies, presenting testable ideas and a new approach for precision cancer treatment. Literature search: PubMed, Scopus, and Web of Science were searched for relevant studies published between January 2000 and March 2026, with emphasis on recent publications (2024-2026) related to neuro-immune interactions in cancer.

Keywords:  Neuro-immune axis; cancer; immune modulators; immunotherapy; novel targets

DOI:  https://doi.org/10.1080/1750743X.2026.2676456
Nature. 2026 May;653(8116): S74-S75

How the connection between lung cancer and the brain could lead to better treatments.

Liam Drew.



Keywords:  Brain; Cancer; Diseases; Neuroscience

DOI:  https://doi.org/10.1038/d41586-026-01458-z
Front Immunol. 2026 ;17 1789297

Peripheral nerve remodeling in the tumor microenvironment: neuro-immune crosstalk, molecular mechanisms, and precision therapeutic.

Huiying Liu, Xunjun Li, Jiang Yu, Tao Chen.

  As a crucial component of the tumor microenvironment, the nervous system modulates tumor initiation, progression, and metastasis. Conversely, tumors actively hijack and reshape neural structures to activate nerve-dependent developmental and regenerative processes that promote their own growth and survival. Despite extensive progress in tumor-neural crosstalk, the molecular mechanisms underlying neuro-immune coordination in peripheral nerve remodeling remain incompletely understood, and integrated strategies targeting this axis to overcome immunotherapy resistance are still lacking. This review comprehensively examines the phenotypic and functional remodeling of the peripheral nervous system within the tumor microenvironment, with a focus on neuro-immune crosstalk between neural cells, immune cells and cancer cells. We systematically analyze phenotypic remodeling in neurons and glial cells, with particular emphasis on autonomic nerve differentiation, functional reprogramming of the neurotrophin family, and the regulatory roles of immune cells in these processes. Finally, we discuss precision therapeutic strategies including β-adrenergic blockades, neurotrophin signaling inhibition, surgical and pharmacological denervation, and combinatorial regimens with immunotherapy, highlighting their translational potential in cancer treatment. Neuro-immune crosstalk in the tumor microenvironment: schematic of four core interaction nodes: This schematic illustrates the bidirectional interactions between peripheral nerves and immune cells within the tumor microenvironment. Schwann cells engage in antigen presentation and cytokine signaling with tumor-associated macrophages and lymphocytes. Sympathetic-derived norepinephrine drives T cell exhaustion and myeloid-derived suppressor cell expansion, while parasympathetic-derived acetylcholine activates α7 nicotinic acetylcholine receptors on immune cells to suppress NF-κB signaling. Macrophage- and lymphocyte-derived NGF and BDNF establish positive feedforward loops that amplify tumor-neural-immune interactions. Together, these interconnected mechanisms support tumor innervation, progression and immune evasion, positioning the neuro-immune axis as an emerging therapeutic target for cancer treatment.

Keywords:  autonomic nerve differentiation; cancer therapeutic strategies; neurotrophin functional reprogramming; peripheral nervous system remodeling; tumor microenvironment; tumor-neural interactions

DOI:  https://doi.org/10.3389/fimmu.2026.1789297
Comput Med Imaging Graph. 2026 May 24. pii: S0895-6111(26)00079-0. [Epub ahead of print]132 102776

An interpretable multimodal model integrating clinical, spectral CT imaging, and deep learning analysis of intra- and peritumoral regions for preoperative prediction of perineural invasion in gastric cancer: A prospective, multicenter study.

Yuncong Zhao, Lihong Chen, Lili Wang, Wenjing Yue, Deye Zeng, Yaru You, Caiming Weng, Weixing Li, Yilin Chen, Lin Lin, Haiping Xu, Yunjing Xue.

   OBJECTIVE: Perineural invasion (PNI) is crucial for risk stratification and treatment planning. This study aims to develop a novel multimodal model for preoperative prediction of PNI in gastric cancer.
METHODS: A total of 250 patients with pathologically confirmed gastric cancer from multiple centers were enrolled and divided into a training cohort (n = 138), an internal validation cohort (n = 59), and an external validation cohort (n = 53). Spectral CT parameters from both intra- and peritumoral regions were acquired using the GSI viewer software, while deep learning features were extracted via a ResNet-50 architecture. Clinical features were screened through univariate and multivariate regression analyses. Based on machine learning, we developed a spectral parameter model, a deep learning feature model, a clinical prediction model, and a multimodal fusion model (MFM). The predictive performance of the models was evaluated using calibration curves, receiver operating characteristic curves, and decision curve analysis (DCA). Model interpretability was achieved by employing Shapley Additive exPlanations (SHAP).
RESULTS: Compared with individual models, MFM demonstrated the best predictive performance, with area under the curve (AUC) values of 0.926, 0.885, and 0.871 in the training, internal validation, and external validation cohorts, respectively. DCA confirmed that MFM provided a higher net benefit over a wide range of threshold probability. Calibration curve showed MFM had better predictive consistency, and the Hosmer-Lemeshow test indicated good fit across all cohorts (all p-values > 0.05). SHAP effectively interpreted the decision-making process of the model.
CONCLUSION: The novel multimodal fusion model, which integrates clinical, spectral CT parameters, and deep learning features from intra- and peritumoral regions, demonstrated outstanding performance in preoperatively predicting PNI in gastric cancer.

Keywords:  Deep learning; Gastric cancer; Peripheral nerve invasion; SHAP; Spectral CT

DOI:  https://doi.org/10.1016/j.compmedimag.2026.102776
Abdom Radiol (NY). 2026 May 26.

The value of extracellular volume based on spectral CT in lymph node metastasis, perineural invasion, and lymphovascular invasion of colon cancer.

Yijie Wang, Jianyao Lu, Yaomin Li, Yaying Yang, Yijun Yu, Zhengyun Sun, Yan Bi, Yuechao Guo, Qiong Zhou, Wenfen Shi, Yamin Li.

   OBJECTIVES: This study aimed to investigate the value of dual-layer detector spectral CT (DLCT)-derived extracellular volume (ECV) in predicting lymph node metastasis (LNM), perineural invasion (PNI), and lymphovascular invasion (LVI) in colon cancer.
METHODS: A total of 120 patients with histopathologically confirmed colon cancer who underwent preoperative DLCT were retrospectively enrolled. Patients were grouped based on pathological status of LNM, PNI, and LVI. Iodine concentration (IC) and effective atomic number (Zeff) were measured across arterial, venous, and delayed phases. Normalized IC (NIC), normalized Zeff (NZeff), and delayed-phase ECV were calculated. Interobserver agreement was assessed using intraclass correlation coefficient (ICC). Univariate and multivariate analyses were performed, and receiver operating characteristic curves were constructed to evaluate diagnostic performance.
RESULTS: Delayed-phase IC, NIC, NZeff, and ECV were significantly higher in LNM-positive, PNI-positive, and LVI-positive groups than in negative groups (all P < 0.05). Venous-phase IC, Zeff, and NIC also differed significantly between LNM and PNI subgroups (all P < 0.05). Delayed-phase ECV achieved the highest AUCs for predicting LNM (0.735), PNI (0.723), and LVI (0.705). Combining ECV with T stage or pathological grading further improved diagnostic efficacy. ICC values indicated excellent interobserver consistency.
CONCLUSION: DLCT-derived delayed-phase ECV serves as a promising non-invasive imaging marker for predicting LNM, PNI, and LVI in colon cancer. Combined with clinical factors, ECV may help improve preoperative risk stratification and assist clinicians in individualized treatment planning.

Keywords:  Colon cancer; Dual-layer detector spectral CT; Extracellular volume; Lymph node metastasis; Lymphovascular invasion; Perineural invasion

DOI:  https://doi.org/10.1007/s00261-026-05572-4
Pharmacol Res. 2026 May 23. pii: S1043-6618(26)00176-3. [Epub ahead of print]230 108261

Neural state as a determinant of tumor immunity in lung cancer.

Jinglu Yu, Jialong Qi, Zujun Que, Xiaoni Kong, Yu Feng.

  Immune checkpoint blockade has reshaped lung cancer therapy, yet durable benefit remains confined to a minority of patients, and resistance often emerges even in initially responsive disease. An increasingly coherent explanation is that neural state-encoded through hierarchical neuroimmune interactions-can profoundly recalibrate anti-tumor immunity and influence treatment responsiveness. In this Review, we synthesize evidence across three integrated levels of neuro-immune regulation in lung cancer. First, lung tumors engage in local neural-immune-tumor interactions, including synapse-like coupling, neuronal mimicry, perineural niches shaped by injury signaling, tumor-induced neurogenesis and neuroendocrine transitions driven by therapy. These local interfaces concentrate catecholaminergic, cholinergic and sensory neuropeptide signaling within spatial microdomains, repeatedly targeting immune bottlenecks. Second, tumor-initiated peripheral-to-central neural circuits link vagal tumor sensing to brainstem autonomic integration, creating a feedback loop that reshapes peripheral immune status. Third, at the systemic level, psychological stress and circadian disruptions impose neuroendocrine constraints through the hypothalamic-pituitary-adrenal axis and sympathetic nervous system, further amplifying immune heterogeneity and clinical variability. By framing "neural state" as a measurable and actionable clinical variable, this unified three-layered neural-immune model clarifies opportunities for patient stratification, mechanism-informed combinations, and neuromodulatory interventions to optimize immunotherapy efficacy in lung cancer.

Keywords:  Immunotherapy resistance; Neuro–immune interactions; Peripheral–central neural circuitry; Stress-induced neuroendocrine modulation; Tumor microenvironment

DOI:  https://doi.org/10.1016/j.phrs.2026.108261
Cancers (Basel). 2026 May 08. pii: 1517. [Epub ahead of print]18(10):

Characterizing Pain in Peripheral Nerve Tumors: Interim Results from a Prospective Bicenter Cohort.

Peripheral Nerve Tumor Study (PNTR) Study Group

  Background/Objectives: This prospective study used a standardized preoperative assessment to characterize the full spectrum of pain in patients with peripheral nerve tumors, addressing the lack of structured pain phenotyping in this population. Methods: Between June 2024 and October 2025, preoperative pain symptoms were assessed in 91 patients, representing 16% of the Peripheral Nerve Tumor Registry (PNTR) cohort, using the PainDETECT questionnaire (0-38) at two centers: University Hospital Ulm, Günzburg (n = 72), and University Hospital Essen (n = 19). Results: Ninety-one patients (61.5% male; mean age, 49 years) were included. Most tumors were located in the lower extremity (54.9%). PainDETECT scores were ≤12 in 51.6%, 13-18 in 24.1%, and ≥19 in 21.9% of patients. Malignant tumors (6.5%) had the highest mean score (17), but benign tumors also showed a relevant pain burden (mean 11.9). Hybrid peripheral nerve sheath tumors and neurofibromas had numerically higher mean scores than schwannomas, although the difference was not statistically significant. Pain severity was not associated with tumor size, depth, or affected nerve. The most common sensory features were electric-shock-like and pressure-related pain, as reflected by a positive Tinel sign in 86.8% of patients. The most frequent pain pattern was intermittent attacks with pain-free intervals (46%). Conclusions: These interim results indicate that pain is common even in benign peripheral nerve tumors, challenging the assumption that these lesions are often asymptomatic. Malignant tumors showed the highest pain scores. The heterogeneous pain phenotypes highlight the need for individualized assessment and management. Expansion to a multicenter evaluation within the framework of the PNTR is planned.

Keywords:  MPNST; PainDETECT; neuropathic pain; pain assessment; peripheral nerve tumor; schwannoma

DOI:  https://doi.org/10.3390/cancers18101517
Cureus. 2026 Apr;18(4): e107751

Large Malignant Peripheral Nerve Sheath Tumor Arising From the Sciatic Nerve in a Patient With Neurofibromatosis Type 1.

Mohammed Benlili, El Abbassi Mohamed, Doha Arreyouchi, Oufkir Ayat Allah.

  Malignant peripheral nerve sheath tumors (MPNSTs) are rare and aggressive soft tissue sarcomas arising from peripheral nerves or through the malignant transformation of preexisting benign nerve sheath tumors, particularly in patients with neurofibromatosis type 1 (NF1). Sciatic nerve involvement is uncommon and presents major diagnostic and surgical challenges because of the risk of significant functional impairment. A 21-year-old man with NF1 presented with a one-year history of a rapidly progressive right thigh mass associated with pain and severe motor deficit of the lower limb. Magnetic resonance imaging showed a large heterogeneous intramuscular mass in the posterior compartment of the right thigh, measuring 167 × 100 × 84 mm, with intratumoral necrotic areas and close continuity with the sciatic nerve. Core needle biopsy confirmed MPNST. After active bleeding developed at the biopsy site, urgent surgical resection was performed. Intraoperatively, the tumor was found to involve the sciatic nerve, particularly its common peroneal division, which required sacrifice during excision. A redundant plexiform neurofibroma on the medial aspect of the thigh was also excised separately. Histopathological examination confirmed the Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade 3 MPNST with negative surgical margins. The patient subsequently received adjuvant radiotherapy and chemotherapy. At the two-year follow-up, there was no evidence of local recurrence or distant metastasis, and neurological status remained stable with rehabilitation. This case highlights the diagnostic complexity and surgical difficulty of giant sciatic nerve MPNST in a patient with NF1. Early recognition, complete surgical resection, and multidisciplinary management are essential to optimize oncologic outcomes.

Keywords:  malignant peripheral nerve sheath tumor; neurofibromatosis type 1; peripheral nerve tumor; sciatic nerve; soft tissue sarcoma

DOI:  https://doi.org/10.7759/cureus.107751
Mol Pain. 2026 May 26. 17448069261456866

EXPRESS: RIN1 inhibited TRPV1-dependent pain sensitization in a mouse model of bone cancer pain.

Yue Zhang, Hai-Feng Jiang, Ya-Ni Guo, Shao-Shan Wang, Xiang-Ru Zeng, Kang-Li Wang, Chaojun Wei, Xiaodong Hu.

  The Ras and Rab interactor 1 (RIN1) is a multifunctional signaling protein that has been implicated in the regulation of tumor cell migration and proliferation. Here we found that RIN1 was abundant in the dorsal root ganglia (DRG) neurons positive for transient receptor potential vanilloid 1 (TRPV1), a critical mediator of pain sensitization in patients with metastatic bone cancer. Our data showed that RIN1 interacted with TRPV1 and induced the endocytosis of TRPV1 through its guanine nucleotide exchange factor activity toward small GTPase Rab5. This process limited the duration and magnitude of TRPV1-dependent acute pain responses in intact male mice. Conditioned knockout of RIN1 in the DRG neurons enhanced TRPV1 activity and led to the reflexive nociceptive sensitization and aversive pain behaviors. In mice with the bone cancer pain, we found a significant reduction of RIN1 protein level in the DRG neurons, which correlated with TRPV1 accumulation on the plasma membrane. Special rescue of RIN1 expression in the DRG neurons repressed the surface TRPV1 distribution and alleviated both the reflexive-defensive and affective-motivational aspects of bone cancer pain. Our data thus revealed an important role of RIN1 in the negative control over TRPV1-dependent pain behaviors.

Keywords:  Bone cancer pain; Dorsal root ganglia; Ras and Rab interactor 1; Transient receptor potential vanilloid 1

DOI:  https://doi.org/10.1177/17448069261456866
Am Soc Clin Oncol Educ Book. 2026 Jun;46(3): e517676

Assessment and Management of Cancer-Related Cognitive Impairment.

Yin Ting Cheung, Mu-Hsing Ho, Joanna Fardell, Janette L Vardy.

Cancer-related cognitive impairment (CRCI) is common and multifactorial in nature with the cancer itself, various treatment modalities, as well as socioenvironmental, biobehavioral, and lifestyle factors all potentially contributing to cognitive impairment in cancer survivors. Estimates of CRCI prevalence vary widely depending on cancer type and the cognitive assessment tools used, but range from 25% to 75%. CRCI typically affects memory, processing speed, attention, and executive function. Diagnosis can be challenging because of a poor association between self-reported cognitive symptoms and performance on standardized neuropsychological assessment. Patient-reported outcome measures are used to assess cognitive symptoms. A comprehensive interview and history-taking by a psychologist or neuropsychologist identifies additional cognitive risk factors and comorbidities, combined with standardized neuropsychological testing, with results compared with normative data. This process evaluates cognitive skills and impairments, including specific affected cognitive domains. Based on the results and the individual concerns of the cancer survivor, tailored management strategies for cognitive impairments can be developed, including advice and support for returning to study or work. There is still inconsistent evidence for the use of pharmacologic agents for CRCI. Education about CRCI and compensatory and supportive strategies may be helpful. Brain training programs have been shown to assist with cognitive symptoms, with variable results for objective cognitive function. Cognitive rehabilitation studies (computer-based training and/or compensatory strategy training) report some improvements in certain studies on some objective cognitive measures, generally memory, as well as improvements in cognitive symptoms. Tai Chi and Qigong have also been found helpful for cognitive symptoms. Lifestyle changes, including a healthy diet, regular exercise, stress management, and addressing sleep disturbances, should be considered.

DOI: https://doi.org/10.1200/EDBK-26-517676