bims-netuvo 2025-12-28 papers

Brain Behav Immun. 2025 Dec 22. pii: S0889-1591(25)00481-7. [Epub ahead of print] 106239

Neural control of Immunotherapy: how Tumor-innervation shapes Anti-Tumor immune responses.

Hatice Satilmis, Adrien Denis, Karin Vanderkerken, Elke De Bruyne, Eline Menu, Erica Sloan, Kim De Veirman.

The role of the sympathetic nervous system (SNS) in cancer biology has gained increasing attention, and its ability to affect immunotherapy is starting to become clearer. Extensive evidence shows that neuro-onco-immune interactions significantly influence tumor progression and the effectiveness of cancer treatments. Blocking SNS signaling, primarily through β-adrenergic receptors, enhances immune cell functions, by increasing CD8+ T-cell activation and cytokine production, while reducing immunosuppressive cell populations. This review explores the relationship between SNS signaling and cancer immunotherapy, emphasizing how SNS activation affects the efficacy of various immunotherapies, including immune modulators, immune checkpoint inhibitors, oncolytic virus therapy, therapeutic vaccines, and CAR-T cell therapies. We summarize retrospective studies investigating the use of β-blockers during immunotherapy, suggesting potential benefits for treatment outcomes of blocking SNS signaling in the tumor microenvironment. We examine ongoing clinical trials that evaluate the use of beta-blockers with immune checkpoint inhibitors, which aim to improve patient outcomes. While translational and preclinical studies provide ample evidence for targeting SNS signaling in cancer immunotherapy, clinical studies are only beginning to emerge. Ultimately, this review underscores the need for further research to better understand how SNS signaling can be targeted to optimize immunotherapy, paving the way for more effective treatment strategies.

Keywords: Adrenergic signaling; Cancer Immunotherapy; Immune microenvironment; Neuro-immune interaction; Sympathetic nervous system; β-blocker

DOI: https://doi.org/10.1016/j.bbi.2025.106239

Exp Mol Med. 2025 Dec 22.

Brain metastasis from non-small cell lung cancer: crosstalk between cancer cells and tumor microenvironment components.

Myung-Seo Kim, Juyoun Lee, Jeong Eun Lee, Jong Hun An, Jun Young Heo, Min-Kyung Yeo.

The majority of patients with lung cancer are diagnosed at an advanced stage, with a substantial proportion exhibiting signs of brain metastases (BMs). BM is associated with debilitating symptoms, including headaches, seizures and neurological or cognitive impairments, which severely impact the quality of life of patients. Despite considerable advancements in lung cancer treatment modalities, the management of BM remains challenging due to the complex cellular and structural nature of the blood-brain barrier and resistance driven by acquired genetic mutations. Non-small cell lung cancer (NSCLC) is characterized by diverse genetic alterations. The application of immunotherapy has successfully enhanced antitumor immune responses within the tumor microenvironment (TME) of affected patients. The intricate interplay between NSCLC cells and the TME plays a critical role in the pathogenesis of BM. This review focuses on the brain-specific TME and its exploitation by tumor cells to establish metastases through strategic, site-specific mechanisms. The reciprocal molecular interactions, immune modulation and adaptation of NSCLC cells to the brain metastatic niche are central to this process. A deeper understanding of the complex crosstalk between tumor cells and TME is essential for devising more effective and targeted therapeutic interventions for BM.

DOI: https://doi.org/10.1038/s12276-025-01604-z

Ann Thorac Surg Short Rep. 2025 Dec;3(4): 954-958

Too Hot? Don't Believe Me, Just Watch: Highly Positron Emission Tomography-Avid Thoracic Schwannomas.

Neelesh Bagrodia, Peter J Kneuertz, Nicholas J Pastis, Desmond M D'Souza, Robert E Merritt, Ioana Baiu.

Schwannomas are benign peripheral nerve sheath tumors with characteristic imaging features and low avidity on positron emission tomography (PET). Transformation into malignant peripheral nerve sheath tumors (MPNSTs) is rare (<0.3%), but it typically manifests with invasive, large (>5 cm), PET-avid, heterogeneous tumors. Although schwannomas may be monitored or excised, MPNSTs require aggressive systemic treatment. We present 2 intrathoracic schwannomas with discordant radiologic and pathologic findings, highlighting the preoperative diagnostic uncertainty. These cases emphasize the critical role of multidisciplinary evaluation in guiding management when high PET avidity suggests malignancy despite benign pathologic features.

DOI: https://doi.org/10.1016/j.atssr.2025.06.013

NeuroSci. 2025 Dec 18. pii: 131. [Epub ahead of print]6(4):

Brain Metastatic Lung Cancer Patients: A Multitarget Therapeutic-Supportive Strategy with Anti-STAT3 Silibinin.

Elisa Roca, Elena Roca, Alessandra Cucinella, Giorgio Madonia, Giovanni Centonze, Fiorella Lombardo, Licia Martinelli, Maria Elisa Damiani, Antonio Santo.

BACKGROUND: Innovative treatments for lung cancer patients have significantly improved their lives. Therefore, patients who develop brain metastases are more likely to require management of quality of life (QoL) by reducing pathological decline in brain function. New therapeutic strategies have allowed us to manage brain metastases, thanks to the ability to cross the blood-brain barrier. Moreover, new molecules have been designed as adjuvants to standard treatments for the management of cancer patients with brain metastases.
METHODS: We implemented a descriptive, observational, retrospective study. Therefore, we consecutively collected the data of eighty-six (N = 86) patients admitted to our department (April 2020-April 2025) diagnosed with brain involvement in a thoracic neoplasm and treated with silibinin, in association with standard treatment. The main endpoint of our analysis is to define the safety profile of silibinin and to evaluate its eventual benefits in terms of QoL.
RESULTS: Silibinin was well tolerated (only one mild adverse event was reported); furthermore, patients taking silibinin had a good quality of life that was maintained over a long period of time, and in some cases, an improvement in neurological symptoms and overall patient well-being was also documented.
CONCLUSIONS: Our study is the first collection of a large number of lung cancer patients with brain metastasis taking silibinin, which is very well tolerated and allows patients to maintain a good QoL.

Keywords: STAT3 (signal transducer and activator of transcription 3); brain metastases; lung cancer; quality of life; silibinin

DOI: https://doi.org/10.3390/neurosci6040131

JMIR Res Protoc. 2025 Dec 23. 14 e78596

Antidepressant and Antipsychotic Drug Use and Cancer Risk: Protocol for an Overview of Systematic Reviews and Meta-Analyses.

Joan Vicent Sánchez-Ortí, Jaume Forés-Martos, Vui Doan, Pablo Vicente-Martínez, Diego Macías Saint-Gerons, María Flores-Rodero, Jon Sánchez-Valle, Patricia Correa-Ghisays, Vicent Balanzá-Martínez, Pau Soldevila-Matías, Joan Vila-Francés, Emilio Soria-Olivas, Alfonso Valencia, Rafael Tabarés-Seisdedos.

BACKGROUND: The relationship between cancer and central nervous system disorders has received increasing attention recently. Consequently, antipsychotics and antidepressants, commonly prescribed for conditions such as depression, bipolar disorder, and schizophrenia, have emerged as potential modulators of subsequent cancer risk. Previous studies have suggested that the use of these medications is associated with a decreased risk of cancer incidence and mortality, making them suitable candidates for drug repurposing. However, the potential therapeutic benefits do not extend to all cancer types, as some data suggest an increased risk for specific tumors.
OBJECTIVE: This study aims to conduct a comprehensive review of systematic reviews and meta-analyses (review of reviews) that assess whether exposure to antidepressants or antipsychotics influences cancer incidence and mortality.
METHODS: To provide a clear overview of this review, we have designed and registered the study protocol. Specifically, we will include systematic reviews and meta-analyses that examine the relationship between previous antipsychotic or antidepressant treatments and the subsequent cancer risk. The primary outcome will be the risk of cancer incidence and mortality (all malignant neoplasms) associated with exposure to psychopharmacological medications. Furthermore, secondary outcomes will include site-specific cancer incidence and mortality (eg, lung cancer). Literature searches will be conducted in multiple electronic databases (from their inception onwards), including PubMed/MEDLINE, Embase, and the Cochrane Database of Systematic Reviews. Three researchers will independently screen all citations, abstracts, and full-text articles. We will perform parallel search, selection, and extraction tasks using a large language model (GPT-4o; OpenAI). Data selection and extraction will involve both human reviewers and GPT-4o, whose performance will be validated through human evaluations. Thus, we will verify whether this type of tool can accelerate or even perform the tasks involved in a systematic review. The risk of bias and the quality of individual studies will be evaluated using appropriate tools. Subsequently, we will extract the summary association measures (eg, pooled relative risk, odds ratio, and hazard ratio) as reported in each included systematic review. Where available, we will summarize subgroup and sensitivity analyses as described by the authors.
RESULTS: Planned searches will be conducted in various electronic databases from their creation until September 2025. No results are available or included in this protocol. The expected results will be published in 2026.
CONCLUSIONS: This overview of systematic reviews and meta-analyses will provide an updated synthesis of the cancer risk associated with antipsychotic and antidepressant drugs. Furthermore, this study will examine factors that may explain potential study variations. Ultimately, these findings will be published in a peer-reviewed journal.
TRIAL REGISTRATION: OSF Registries 10.17605/OSF.IO/5ACWH; https://osf.io/5acwh/overview.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/78596.

Keywords: antidepressants; antipsychotics; cancer; drug repurposing; large language models; meta-analysis; systematic review

DOI: https://doi.org/10.2196/78596

Neurology. 2026 Jan 27. 106(2): e214490

Memory Deficits in Cancer Patients With Serum NMDA Receptor Autoantibodies.

Frederik Bartels, Andreea Tapuc, Kristin Rentzsch, Sophie L Duong, Harald Prüss, Carsten Finke.

OBJECTIVES: Neuronal autoantibodies are linked to cognitive impairment in neurologic diseases and can be associated with tumors. In patients with cancer, IgA/IgM N-Methyl-D-Aspartate receptor (NMDAR) autoantibodies are most common, yet their clinical relevance is unclear. We assessed cognitive function in cancer patients with serum NMDAR autoantibodies and compared the results with matched controls.
METHODS: For this cross-sectional case-control study in Germany, we recruited 1,055 patients with cancer and tested for neuronal serum autoantibodies. Cognitive assessment was performed blinded to antibody status and after excluding patients with potential confounders of cognitive dysfunction. The tests included verbal memory (Rey Auditory Verbal Learning Test), visuospatial memory (Rey-Osterrieth Complex Figure), and working memory.
RESULTS: Fifty-six patients with IgA/IgM NMDAR autoantibodies (median age 61.0 years [28.0-86.0], 35.7% female) were matched 1:1 to autoantibody-negative patients by age, sex, cancer type, and stage. Autoantibody-positive patients showed impairments in verbal memory (mean score ± SD: 9.7 ± 3.6 vs 11.4 ± 3.2; p = 0.01; Cohen d = 0.49), visuospatial memory (19.4 ± 7.0 vs 22.6 ± 5.6; p = 0.01; d = 0.50), and working memory (6.2 ± 1.9 vs 7.0 ± 2.1; p = 0.04; d = 0.40). Memory function decreased with increasing IgA NMDAR autoantibody levels. Both groups performed similarly on measures of attention, executive function, and verbal fluency.
DISCUSSION: Serum NMDAR autoantibodies are associated with isolated memory deficits in patients with cancer and might serve as a potential biomarker for cancer-related cognitive impairment.

DOI: https://doi.org/10.1212/WNL.0000000000214490