Neuro-oncology最新文献

{"title":"Biomarker-guided and systemic treatment strategies for meningioma.","authors":"Sylvia C Kurz, Matthias Preusser","doi":"10.1093/neuonc/noag071","DOIUrl":"https://doi.org/10.1093/neuonc/noag071","url":null,"abstract":"<p><p>Meningiomas represent the most common intracranial tumors, overall. While a majority of tumors can be considered indolent, a subset of patients will experience repeated recurrences despite surgical and radiotherapeutic interventions. For these patients, there are only a limited number of promising systemic therapy options available. Effective drug development for meningiomas has been limited by variability in trial design, the clinical trial endpoints being used across studies, heterogeneous tumor biology and patient selection in clinical trials, and inconsistent radiological response assessment criteria. However, over the past years, tremendous progress has been made in understanding the biological and molecular underpinnings of meningiomas. Guidance on clinical trial endpoints and response assessment criteria has also improved clinical trial design and it is widely recognized that patient participation in a clinical trial remains the best way to evaluate novel therapy options and move drug development forward. In this review, we discuss factors of optimal clinical trial design for meningioma clinical trials and review and discuss the evidence supporting the use of various contemporary biomarker-guided and systemic therapy options for patients with meningioma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarker-guided immunotherapies for primary CNS tumors.","authors":"Lukas Bunse, Theresa Bunse, Isabel Poschke, Robert M Prins, Michael Lim, Michael Platten","doi":"10.1093/neuonc/noag116","DOIUrl":"https://doi.org/10.1093/neuonc/noag116","url":null,"abstract":"<p><p>Refined immunotherapeutic modalities for the treatment of primary central nervous system (CNS) tumors - vaccines, virotherapies, immune checkpoint inhibitors, and cell therapies - are starting to show efficacy in selected patients with primary CNS tumors. Still most patients do not derive a meaningful clinical benefit, despite evidence of biological activity. While the unique immunosuppressive environment of the CNS, cellular heterogeneity and brain borders prohibiting access present substantial challenges for effective treatment, there is a need to define robust biomarkers for response to immunotherapies. As immunotherapies critically depend on multiple tumor intrinsic as well as host factors, this task is substantially more challenging than defining biomarkers for response to targeted therapies. Recent advances in biomarker identification and characterization for immunotherapies have opened new avenues for precision immunotherapy approaches. This review examines the current state of biomarker-guided immunotherapy for primary CNS tumors, focusing on key biomarkers including immunogenic antigens, HLA ligandomics, tumor immune microenvironment characteristics, cell-free DNA, tumor mutational burden, and T cell populations in tumor tissue, blood, and cerebrospinal fluid. We discuss how these biomarkers can guide the selection and optimization of immunotherapeutic strategies including cancer vaccines, T cell therapy, and immune checkpoint inhibitors particularly for glioblastoma, and highlight current challenges and future directions in the field.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Re: Schreck et al. - Critical considerations for BRAF-altered tumors in children.","authors":"Michael Wyld, Eric Bouffet, Jordan R Hansford, Matthias A Karajannis","doi":"10.1093/neuonc/noag247","DOIUrl":"https://doi.org/10.1093/neuonc/noag247","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuron activity-dependent cancer progression.","authors":"Justin Nelson, Khalil Ali Ahmad Kasm, Yuan Pan, Kathryn R Taylor","doi":"10.1093/neuonc/noag214","DOIUrl":"https://doi.org/10.1093/neuonc/noag214","url":null,"abstract":"<p><p>Neuronal activity instructs a broad range of biological processes, including the regulation of cancers of both the central and peripheral nervous systems. Studies across multiple cancer types have established that neuronal activity regulates tumor progression through diverse mechanisms, including direct synaptic communication, neurotransmitter and neuropeptide signaling, activity-dependent paracrine signaling, and bioelectrical signaling. In turn, tumors actively remodel neural circuits through altered neuronal excitability, axonogenesis, neuronal reprogramming, and nerve injury, establishing bidirectional interactions that reinforce malignant progression. Importantly, neural regulation of cancer is highly context-dependent, with the same neural circuits exerting tumor-promoting or tumor-restraining effects depending on the cancer type, disease stage, neuronal subtype, and surrounding microenvironment. Neuron-tumor interactions engage diverse cellular components of the tumor microenvironment, including immune, stromal, vascular, and glial cells, extending neural regulation beyond direct effects on cancer cells. Communication between peripheral tumors and the central nervous system further reveals organism-wide neural regulation of cancer. Together, these findings establish neuronal activity as a fundamental regulator of tumor biology and highlight neuron-cancer signaling and neuromodulation as promising therapeutic targets across diverse malignancies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149149902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to Wyld et al.","authors":"Sebastien Perrault, Jean M Mulcahy Levy, Marjolein Geurts, Karisa C Schreck, Sabine Mueller","doi":"10.1093/neuonc/noag248","DOIUrl":"https://doi.org/10.1093/neuonc/noag248","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting hypoxia-driven histone lactylation in myeloid cells synergizes with CD137 agonism to expand effector-like exhausted CD8+ T cells in glioblastoma.","authors":"Alessio Ugolini, Fabio Scirocchi, Alessandra De Leo, Filippo Badii, Xiaoxian Liu, Angelica Pace, Luca D'Angelo, James K C Liu, Arnold B Etame, Pulak Ray, Marianna Nuti, Antonio Santoro, Aurelia Rughetti, Michael A Vogelbaum, Xiaoqing Yu, Filippo Veglia","doi":"10.1093/neuonc/noag226","DOIUrl":"https://doi.org/10.1093/neuonc/noag226","url":null,"abstract":"<p><strong>Background: </strong>Overwhelming presence of immunoregulatory myeloid cells and dysfunctional T cells is a major barrier to effective immunotherapies in glioblastoma (GBM). Therapeutic strategies that simultaneously address myeloid-driven immunosuppression and impaired T cell function are therefore needed to restore antitumor immunity in GBM.</p><p><strong>Methods: </strong>We employed single-cell RNA sequencing, immunophenotyping, and functional analyses in an orthotopic murine GBM model (SB28) to investigate how hypoxia shapes the tumor immune microenvironment and limits CD8+ T cell responses. Pharmacologic hypoxia modulation using low-dose axitinib was combined with therapeutic intervention targeting CD137 in two GBM models (SB28, CT2A).</p><p><strong>Results: </strong>Monocyte-derived macrophages (MDMs) and neutrophils constitute the most abundant and functionally immunosuppressive myeloid subsets within the GBM TME. Hypoxia reprogrammed MDMs and neutrophils into immunosuppressive cells, limiting the expansion of CD8+ T cells. Low-dose axitinib reduced intratumoral hypoxia, leading to altered glucose uptake and histone lactylation in MDMs and neutrophils, thereby impairing their immunosuppressive function and promoting the expansion of intratumoral PD-1+CD137+CD8+ T cells, specifically in the SB28 model. CD137 is largely expressed by effector-like exhausted CD8+ T cell subsets (EX-eff). Agonistic targeting of CD137, in combination with axitinib, robustly expanded EX-eff, which was accompanied by durable tumor regression, immunological memory, and long-term survival. Additionally, the abundance of PD-1+CD137+CD8+ T cells correlated with improved disease-free survival in patients with GBM.</p><p><strong>Conclusion: </strong>Together, these findings establish a rationale for a combinatorial strategy that couples myeloid cells targeting and CD8+ T cell activation to overcome immunotherapy resistance in GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circadian biology in brain cancer diagnosis and treatment.","authors":"Sofia V Salvatore, Annika M Kaval, Erin M Gibson, Erik D Herzog","doi":"10.1093/neuonc/noag179","DOIUrl":"https://doi.org/10.1093/neuonc/noag179","url":null,"abstract":"<p><p>Glioblastoma (GBM), the most common and lethal primary brain cancer, has a median survival of 15 months. Despite repeated efforts over 20 years to introduce life-extending therapies, little has changed in the standard of care. Recent studies have revealed that GBM cells express daily rhythms in gene expression and sensitivity to chemotherapy. In this review, we highlight the role of circadian biology in GBM growth, and its potential applications to GBM diagnosis and treatment. The hallmarks of cancer often show daily variation. We emphasize opportunities to advance our understanding of glioblastoma pathophysiology by considering how brain tumors integrate into the host circadian system and respond to daily rhythms in neuronal, paracrine, or hormonal signals to promote growth. Circadian treatment strategies include disrupting daily rhythms in GBM cells, blocking their synchronization to the host, or finding best times of day for biopsy, surgery, radiation, or chemotherapy. We discuss an ongoing temozolomide chronotherapy trial in the context of recent evidence against chronotherapy and suggest ways to critically assess time-of-day effects in GBM. With over 500 active clinical trials for GBM, it is time to evaluate, and control for, circadian rhythms in care for brain cancer patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Socioeconomic status and longitudinal neurocognitive outcomes following childhood brain tumour diagnosis: a Swedish national population-based cohort study.","authors":"Jessica Beamish, Edvard de Fine Licht, Petra Boström, Jonas Lödén, Joukje Willemsen, Hanna Mogensen, Ingrid Tonning Olsson, Marita Partanen","doi":"10.1093/neuonc/noag253","DOIUrl":"https://doi.org/10.1093/neuonc/noag253","url":null,"abstract":"<p><strong>Background: </strong>Lower socioeconomic status (SES) is linked to poorer neurocognitive development in the general population, but these effects in paediatric brain tumour survivors are underexplored. We examined the relationship between parental SES, clinical factors, and neurocognitive functioning longitudinally up to five years post-diagnosis and determined if young children were more vulnerable.</p><p><strong>Methods: </strong>This population-based registry study included Swedish children diagnosed with brain tumours between 2008-2023 and who completed ≥2 neurocognitive assessments. Parental education, occupation and household income were used as individual SES indicators as well as a combined SES measure. Linear mixed models examined relationships between SES and age at diagnosis on neurocognitive outcomes, accounting for time since diagnosis, chemotherapy, and radiotherapy.</p><p><strong>Results: </strong>We included 461 children (mean age at diagnosis=7.98 years, SD=4.01). Higher SES was associated with higher neurocognitive z-scores on processing speed (B=0.23), working memory (B=0.25), nonverbal reasoning (B=0.29), verbal reasoning (B=0.41), and global cognition (B=0.42; q's≤ .039). No interactions between SES and age or time were observed. Longer time since diagnosis was associated with lower processing speed (B=-0.04) and verbal reasoning (B=-0.05, q's≤.041). Younger age at diagnosis was related to steeper declines in nonverbal reasoning (B=0.01, q=.016). Cranio-spinal irradiation was related to lower processing speed (B=-0.50, q=.019).</p><p><strong>Conclusions: </strong>In Swedish childhood brain tumour survivors, lower SES was associated with poorer neurocognitive functioning over time. Absence of socioeconomic differences in rate of decline suggests that lower SES may reduce baseline cognitive reserve rather than amplifying disease or treatment-related toxicity.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CEBPB integrates OSM signaling and eIF4G2-mediated alternative translation to configure enhancer landscape and sustain oncogenic CHI3L1 in glioblastoma.","authors":"Jiyang Liu, Ying Zhang, Xiaoping Yi, Long Xie, Xingze Huang, Zhipeng Zhu, Zhongyuan Zhang, Jing Wang, Suya Zheng, Yongjie Wang, Hangzhe Xu, Yue Yu, Zeming Tan, Tuan Zea Tan, H Phillip Koeffler, Ye Chen, Liang Xu","doi":"10.1093/neuonc/noag246","DOIUrl":"https://doi.org/10.1093/neuonc/noag246","url":null,"abstract":"<p><strong>Background: </strong>CEBPB is a critical driver of mesenchymal transformation and aggressiveness in glioblastoma (GBM). However, fundamental questions remain regarding its dynamic regulation within the GBM microenvironment and its precise mechanistic role in orchestrating the epigenetic and transcriptional reprogramming.</p><p><strong>Methods: </strong>To decode the CEBPB cistrome and its role in chromatin remodeling in GBM, we performed an integrated analysis of CEBPB/H3K27ac ChIP-seq, CEBPB HiChIP, and RNA-seq. Transcriptional and translational control of CEBPB expression was delineated through enhancer profiling, bioinformatics analysis, siRNA screening, synthetic reporter assays, and immunoblotting. Functional investigations were conducted using patient-derived tumor spheroids, human and murine glioma cell lines, and xenograft/allograft murine models.</p><p><strong>Results: </strong>We demonstrate that CEBPB is a super-enhancer-driven gene, with all three isoforms (LAP1, LAP2, LIP) over-expressed in primary GBM. Functional analyses reveal that LAP1 and LAP2 are essential for tumorigenesis, while LIP specifically promotes in vivo growth in a LAP1/LAP2-dependent manner. We further reveal that myeloid-derived OSM potently induces CEBPB expression through OSMR-STAT3-mediated transcription and a novel eIF4G2-dependent alternative translation process. Mechanistically, eIF4G2 directs selective LIP synthesis by engaging a specialized 3'UTR translation enhancer within the CEBPB transcript. Genetic ablation of EIF4G2 suppresses tumorigenicity, a phenotype fully rescued by LIP overexpression. Ultimately, CEBPB isoforms coordinately rewire the epigenetic landscape, remodeling super-enhancers and chromatin looping to establish an oncogenic transcriptional program that activates key effectors like CHI3L1.</p><p><strong>Conclusions: </strong>This work elucidates a pathogenic axis in glioblastoma wherein OSM signaling and eIF4G2-mediated alternative translation converge on CEBPB isoforms to enforce enhancer architectures and chromatin interactions for oncogenic transcription.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137165","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFRvIII: An old oncogenic target gets a model built for the immunotherapy era.","authors":"Sarah A Best, James R Whittle, David D Eisenstat","doi":"10.1093/neuonc/noag249","DOIUrl":"https://doi.org/10.1093/neuonc/noag249","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}