bims-netuvo Biomed News
on Nerves in tumours of visceral organs
Issue of 2026–07–26
eight papers selected by
Maksym V. Kopanitsa, Charles River Laboratories
  1. Crosstalk Between Schwann Cells and CD4+ T Cells Promotes Perineural Invasion in Colorectal Cancer.
  2. Multiparametric MRI-based multi-channel deep learning model for accurate preoperative prediction of perineural invasion in lymph node-negative rectal cancer.
  3. [Interpretable machine learning models for preoperative precision prediction of perineural invasion in cervical cancer to support treatment decision: a multicenter retrospective study].
  4. A self-amplifying nerve-fibroblast circuit drives colorectal cancer progression.
  5. Survival benefit of concurrent beta-blocker use in cancer patients treated with radiotherapy: A systematic review and meta-analysis.
  6. Pre-treatment cognitive impairment in patients with NSCLC: Prevalence and psychosocial factors.
  7. Medical Management of Non-Small Cell Lung Cancer Brain Metastases in the Modern Era.
  8. Lurbinectedin in treating CNS metastases from small cell neuroendocrine prostate cancer-a case report.
  1. Cancer Res. 2026 Jul 23.
    Crosstalk Between Schwann Cells and CD4+ T Cells Promotes Perineural Invasion in Colorectal Cancer.
    Huayuan Liu, Yiqiao Deng, Yi Yang, Junshuai Xue, Nuersimanguli Maimaitiming, Bingzhi Wang, Yujing Xin, Jinxue Zhou, Xiaomeng Liu, Chengyao Guo, Lang Yang, Zhen Huang, Haitao Zhou, Jianqiang Cai, Hong Zhao.
      Perineural invasion (PNI) is a common pathological feature associated with poor prognosis of colorectal cancer (CRC). A better understanding of the mechanisms underlying PNI formation could help identify potential strategies to inhibit tumor progression. Here, we revealed an integral role of CD4+ T cells in the development and progression of PNI in CRC. Single-cell RNA sequencing, spatial transcriptomics, and multiplex immunohistochemistry profiling uncovered a distinct HSPA6+CD4+ T cell subset expressing T stress (Tstr) cell markers in CRC PNI tissues. Schwann cells (SCs) colocalized with the HSPA6+CD4+ Tstr cells in PNI, and functional studies showed that SCs promoted Tstr cell differentiation while Tstr cells enhanced SC migration. Interaction between SCs and CD4+ T cells activated the MAPK pathway in SCs and the JAK-STAT pathway in Tstr cells, and inhibition of MAPK and STAT signaling suppressed nerve invasion of CRC cells in vivo. Moreover, SCs in contact with tumor cells possessed the ability to recruit CD4+ T cells; tumor-derived TNF-α stimulated SCs to secrete CCL4, thereby recruiting CD4+ T cells toward SCs. The anti-TNF-α monoclonal antibody infliximab reversed the pro-invasive and pro-migratory effects of SCs on CRC cells and reduced intratumoral CD4+ Tstr cells, and the combination of infliximab with anti-PD-1 treatment produced a combinatorial tumor suppressive effect. Together, this study suggests that SCs near CRC tissues recruit CD4+ T cells and promote their conversion to CD4+ Tstr cells to establish an immunosuppressive microenvironment and simultaneously enhance the migration and tumor-promoting capabilities of SCs, thereby accelerating PNI development.
    DOI:  https://doi.org/10.1158/0008-5472.CAN-25-5781
  2. Abdom Radiol (NY). 2026 Jul 22.
    Multiparametric MRI-based multi-channel deep learning model for accurate preoperative prediction of perineural invasion in lymph node-negative rectal cancer.
    Dalin Cheng, Jingjing Zhao, Zhanhong Liu, Hao Liu, Rui Xue, Ru Bai, Haowen Yang, Kai Ma.
       OBJECTIVE: To develop a multiparametric MRI-based multi-channel deep learning model for accurate preoperative prediction of perineural invasion (PNI) in patients with lymph node-negative rectal cancer (RC).
    METHODS: This multicenter diagnostic study retrospectively enrolled 266 patients with RC from two institutions. Pretreatment multiparametric MRI sequences (T2WI, DWI, and CE-T1WI) were preprocessed, and for each sequence, the ROI was cropped into four views (roi-only, roi-all, enlarge-roi, and no-crop), which were then stacked into a 12-channel input for deep learning. Fusion across the four image sets generated five deep learning (DL) models, along with one hybrid radiomics-deep learning (DLR) model. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC, with stability assessed by stratified bootstrap resampling of 1,000 iterations), sensitivity, specificity, calibration curves, and decision curve analysis (DCA). The DeLong test with Bonferroni correction was used for pairwise model comparisons.
    RESULTS: The dataset was divided into a training cohort (n = 134, Institution 1), an internal validation cohort (n = 58, Institution 1), and an external test cohort (n = 74, Institution 2). In the external test cohort, the conventional radiomics model achieved an AUC of 0.677 (95% CI: 0.412-0.941). The best-performing deep learning image model achieved an AUC of 0.843 (95% CI: 0.680-1.000). The combined DLR model further improved performance, demonstrating strong predictive ability, with AUCs of 0.928 (95% CI: 0.862-0.994) in the training cohort, 0.896 (95% CI: 0.797-0.995) in the internal validation cohort, and 0.863 (95% CI: 0.695-1.000) in the external test cohort. Bootstrap resampling (1,000 iterations) confirmed the stability of the DLR model, yielding consistent mean AUCs across all cohorts.
    CONCLUSIONS: This novel approach integrating radiomics features extracted from multiparametric MRI with multi-channel deep learning enables accurate preoperative prediction of PNI in RC, providing valuable support for individualized treatment planning and prognostic evaluation.
    Keywords:  Deep learning; Magnetic resonance imaging; Perineural invasion; Radiomics; Rectal cancer
    DOI:  https://doi.org/10.1007/s00261-026-05675-y
  3. Nan Fang Yi Ke Da Xue Xue Bao. 2026 Jul 20. pii: 1673-4254(2026)07-1509-11. [Epub ahead of print]46(7): 1509-1519
    [Interpretable machine learning models for preoperative precision prediction of perineural invasion in cervical cancer to support treatment decision: a multicenter retrospective study].
    Mengxin Zhu, Xiao Liu, Shan Zhao, Xin Zhang, Chao Liu, Xiankong Liu, Haochen Qi, Tiesheng Han, Dong Ma.
       OBJECTIVES: To develop an interpretable machine learning model and web-based prediction tool for preoperative risk assessment of perineural invasion (PNI) in cervical cancer.
    METHODS: A total of 845 cervical cancer patients undergoing radical surgery at Fourth Hospital of Hebei Medical University were retrospectively enrolled and divided into training and testing sets in a 7:3 ratio, with another 223 cervical cancer patients at Hebei Medical University Second Hospital during the same period serving as the external validation cohort. LASSO regression identified 13 preoperative predictors, which were incorporated into 7 machine learning algorithms. Model performance was evaluated using AUC and decision curve analysis. The optimal model was interpreted using SHAP values and deployed as a web-based prediction tool.
    RESULTS: Of the total of 1068 patients enrolled, 192 (17.98%) were diagnosed to have PNI. Thirteen preoperative features, namely lymphovascular space invasion (LVSI), depth of stromal invasion, lymph node metastasis (LNM), colposcopy-directed biopsy (CDB), tumor maximum diameter, carcinoembryonic antigen, SCC-Ag, platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-albumin-neutrophil ratio (LANR), menopausal status, age, and histological type were selected. Comparison of model performance revealed that the Extreme Gradient Boosting (XGBoost) model resulted in the best efficacy in both the training and testing datasets with AUC of 0.962 and 0.923 (95% CI: 0.942-0.979 and 0.874-0.960), sensitivity of 0.873 and 0.767, and specificity of 0.939 and 0.942, respectively. Decision curve analysis demonstrated greater net benefit of the XGBoost model across a broader threshold range. The SHAP-XGBoost model showed excellent performance in external validation with an AUC of 0.924 and an accuracy of 0.933.
    CONCLUSIONS: The interpretable SHAP-XGBoost model effectively predicts PNI risk preoperatively. The predictive website derived from this model provides an useful tool to facilitate clinical decision-making in cervical cancer treatment.
    Keywords:  cervical cancer; machine learning; perineural invasion
    DOI:  https://doi.org/10.12122/j.issn.1673-4254.2026.07.05
  4. Cancer Cell. 2026 Jul 24. pii: S1535-6108(26)00305-3. [Epub ahead of print]
    A self-amplifying nerve-fibroblast circuit drives colorectal cancer progression.
    Hiroki Kobayashi, Tadashi Iida, Yosuke Ochiai, Akihiro Sakai, Ruth A White, Yi Zeng, Xiaofei Zhi, Jin Qian, Feijing Wu, Biyun Zheng, Junya Arai, Masahiro Hata, Hualong Zheng, Puran Zhang, Shuang Li, Quin T Waterbury, Jonathan S LaBella, Harry Nagendra, Leah B Zamechek, Atsushi Ogura, Mitsuro Kanda, Holger K Eltzschig, Susan L Woods, Daniel L Worthley, Atsushi Enomoto, Timothy C Wang.
      Nerves and cancer-associated fibroblasts (CAFs) have each been shown to regulate cancer progression directly. However, whether these cells interact to control tumor progression remains largely unknown. We show that in colorectal cancer (CRC), cholinergic stimulation induces CHRM3/Gq-dependent NTN1 secretion from CAFs, which in turn enhances intratumor cholinergic innervation. Within this feedforward loop, cholinergic stimulation promotes CRC growth directly through tumoral CHRM3/Gq-mediated YAP activation, while CAF-derived NTN1 promotes CRC growth and epithelial-to-mesenchymal transition-like programs via UNC5B-PI3K/AKT signaling. Chemogenetic activation of cholinergic neurons or fibroblast activation of the M3 receptor/Gq promotes tumoral YAP and AKT signaling and CRC progression. Conversely, blocking CHRM3 or NTN1 suppresses these pathways and improves mouse survival. In human CRC, high NTN1 expression is associated with a mesenchymal-like subtype and poor patient outcomes. These findings suggest that the neuro-mesenchymal interaction is central to CRC progression and could be therapeutically targeted with a CHRM3 antagonist or NTN1-blocking antibody.
    Keywords:  EMT; Netrin-1; Netrin-1 antibody NP137; acetylcholine; cancer neuroscience; cholinergic nerves; colorectal cancer; epithelial-to-mesenchymal transition; fibroblasts; muscarinic receptor 3; tumor microenvironment
    DOI:  https://doi.org/10.1016/j.ccell.2026.06.018
  5. Medicine (Baltimore). 2026 Jul 24. 105(30): e49582
    Survival benefit of concurrent beta-blocker use in cancer patients treated with radiotherapy: A systematic review and meta-analysis.
    Wentong Xu, Yong Xin, Xue Yang, Mengyang Wu, Hengchang Chen, Xinyu Lu, Yilong Guo, Dehong Yu, Fengjuan Zhou.
       BACKGROUND: Both preclinical and retrospective studies have implicated β-adrenergic signaling in cancer progression, leading to interest in β-blockers (BBs) as adjunctive anticancer agents. There is evidence that they may enhance the sensitivity of cancer cells to radiotherapy and other conventional therapies. We conducted a systematic review and meta-analysis to explore the radiosensitizing effects of BBs.
    METHODS: PubMed, the Cochrane Library, Embase, Web of Science, the China National Knowledge Infrastructure, the China biology medicine database, Wan fang Data, and the VIP database were searched for articles in both English and Chinese from the establishment of the databases to September 8, 2025, to identify studies comparing outcomes according to beta-blocker use (yes vs no) in patients with solid tumors treated with radiotherapy. The primary endpoint was overall Survival (OS), Secondary objectives included 1, 2, 5-Year Survival, disease-free survival, distant metastasis-free survival, locoregional progression-free survival and progression-free survival (PFS).
    RESULTS: 8 studies (3165 patients), including 7 retrospective cohort studies and 1 randomized controlled trial, were analyzed. The most common cancer was non-small cell lung cancer (n = 5). BB use was associated with significantly improved OS (hazard ratio [HR] 0.73, 95% confidence interval: 0.64-0.83). Benefits were also observed for disease-free survival (HR 0.69) and Distant Metastasis-Free Survival (HR 0.62), indicating reduced recurrence and metastasis.
    CONCLUSION: In this meta-analysis, the use of BBs during or around radiotherapy may be associated with longer OS in cancer patients, suggesting that it may enhance the efficacy of radiotherapy and provide a survival benefit. Alternatively, the effect of β-blockers on survival may shift from a nonspecific effect to an intriguing cancer-specific effect over time. Beta-blockers are an intriguing option to explore in prospective studies of patients with solid tumors undergoing radiotherapy.
    Keywords:  beta blockers; cancer survival outcome; radiotherapy; radiotherapy–drug interaction
    DOI:  https://doi.org/10.1097/MD.0000000000049582
  6. IBRO Neurosci Rep. 2026 Dec;21 316-323
    Pre-treatment cognitive impairment in patients with NSCLC: Prevalence and psychosocial factors.
    Benedetta Capetti, Lorenzo Conti, Jenny Luisi, Serena Sdinami, Chiara Marzorati, Roberto Grasso, Samuele Frassoni, Vincenzo Bagnardi, Matteo Chiari, Monica Casiraghi, Gabriella Pravettoni.
       Background: Cancer-related cognitive impairment (CRCI) is increasingly recognized in patients with non-central nervous system malignancies, including non-small cell lung cancer (NSCLC), although evidence on pre-treatment cognitive functioning and associated psychosocial factors remains limited. This exploratory study investigated baseline cognitive functioning in NSCLC patients before oncological treatment and examined the role of cognitive reserve, emotional distress, sleep quality, and subjective cognitive complaints.
    Methods: Fifty NSCLC patients underwent comprehensive neuropsychological and psychological assessment before treatment initiation. Cognitive functioning was evaluated through standardized tests assessing global cognition, executive functions, memory, attention/processing speed, and language. Cognitive impairment was classified according to International Cognition and Cancer Task Force criteria. Psychological measures included subjective cognitive complaints, depressive symptoms, anxiety, sleep quality, cognitive reserve, and quality of life. Associations with a Composite Cognitive Score (CCS) and domain-specific scores were examined using univariable linear regression analyses.
    Results: Eighteen patients (36%) met criteria for objective cognitive impairment at baseline. Higher cognitive reserve was associated with better global cognitive performance and stronger attention/processing speed and executive functioning. Conversely, depressive symptoms, anxiety, and poorer sleep quality were associated with lower CCS and worse performance across several domains, particularly global cognition, memory, and attention/processing speed. Subjective cognitive complaints showed partial concordance with objective cognitive performance.
    Conclusions: Cognitive impairment may already be present in a substantial proportion of NSCLC patients before treatment initiation. Early cognitive and psychosocial assessment may help identify patients at higher risk for CRCI and guide supportive interventions. These findings support early multidisciplinary screening strategies targeting vulnerable patients before treatment.
    Keywords:  Cancer-related cognitive impairment; Cognitive reserve; Neuropsychological assessment; Non-small cell lung cancer; Psychological distress
    DOI:  https://doi.org/10.1016/j.ibneur.2026.07.007
  7. Cancer J. 2026 Jul-Aug 01;32(4):pii: e0840. [Epub ahead of print]32(4):
    Medical Management of Non-Small Cell Lung Cancer Brain Metastases in the Modern Era.
    Benjamin Y Lu, Sarah B Goldberg.
      Brain metastases are a common complication among patients with non-small cell lung cancer and are historically associated with significant morbidity and limited survival. Although surgery and radiation therapy remain essential pillars in the clinical management of brain metastases, the development of several pharmacologic agents with activity in the central nervous system has broadened the role of systemic therapies for treating brain metastases. There is accumulating evidence that, in the appropriate clinical scenarios, systemic therapies may be used to manage both intracranial and extracranial disease while delaying local therapy and mitigating potential treatment-related morbidity. Determining the optimal treatment approach requires careful consideration of the intracranial tumor burden, location of lesions, pathologic and molecular profile, local and systemic therapy options, and overall prognosis. This review will provide updates on the medical management of non-small cell lung cancer brain metastases, with a focus on recent advances in systemic therapy options.
    Keywords:  Brain Metastases; central nervous system; chemotherapy; immunotherapy; non–small cell lung cancer; targeted therapies
    DOI:  https://doi.org/10.1097/PPO.0000000000000840
  8. Front Oncol. 2026 ;16 1840883
    Lurbinectedin in treating CNS metastases from small cell neuroendocrine prostate cancer-a case report.
    Avani Gunuganti, Vedin Barve, William J Kelly, Vijay Gunuganti, Andrew Brenner.
       Background: De novo neuroendocrine prostate cancer is an aggressive, androgen receptor-independent subtype of prostate cancer with poor prognosis. Central nervous system (CNS) metastases from de novo neuroendocrine prostate tumors are rare, and evidence guiding treatment is limited. Lurbinectedin, approved for small cell lung cancer (SCLC), has shown activity in neuroendocrine tumors, though CNS-specific data remain sparse.
    Case presentation: A 57-year-old man presenting with tenesmus, dyschezia, and urinary retention was diagnosed with high-grade neuroendocrine prostate carcinoma with low prostate-specific antigen (PSA) and high proliferative index. Genomic profiling revealed alterations in ATM and BRCA2 and was negative for Rb1 and TP53. He achieved complete systemic response following platinum-based chemoradiotherapy and immunotherapy but later developed multifocal brain metastases with suspected leptomeningeal involvement.
    Intervention and outcomes: After progression on whole-brain radiotherapy and topotecan, lurbinectedin was initiated. Imaging demonstrated marked intracranial response, including resolution and reduction of multiple lesions. Disease progression occurred after six cycles.
    Discussion: This case underscores similarities between neuroendocrine prostate carcinoma and SCLC, supporting the use of SCLC-based therapies. The observed response suggests that lurbinectedin may have clinically meaningful CNS activity, even after failure of standard CNS-directed treatments.
    Conclusion: Lurbinectedin may be a therapeutic option in CNS-dominant neuroendocrine prostate carcinomas. Further studies are needed to better define its intracranial efficacy and durability of response.
    Keywords:  CNS metastasis; lurbinectedin; neuroendocrine; prostate cancer; small cell lung cancer
    DOI:  https://doi.org/10.3389/fonc.2026.1840883
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