Neuro-oncology最新文献

{"title":"BRAF-altered glioma in children and adults: From soup to nuts.","authors":"Vijay Ramaswamy, Uri Tabori","doi":"10.1093/neuonc/noag191","DOIUrl":"10.1093/neuonc/noag191","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2336-2337"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induced pluripotent stem cell-derived natural killer cell therapy induces durable responses in glioblastoma and overcomes resistance via a B7-H3-targeted tri-specific killer engager.","authors":"Jian-Fang Ning, Zachary B Davis, Qudsia Zeb, Peter Hinderlie, Katie Tuininga, Liangjun Wang, Shivani Chaudhary, Young Vue, Jun Ma, Shan Zhu, Ying Zhang, Zachary J Seeman, Karl-Johan Malmberg, Bahram Valamehr, David A Largaespada, Nicholas Zorko, Martin Felices, Frank Cichocki, Jeffrey S Miller, Clark C Chen","doi":"10.1093/neuonc/noag154","DOIUrl":"10.1093/neuonc/noag154","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma is the most aggressive primary brain tumor, with a poor prognosis and limited treatment options. Natural killer (NK) cell therapy is a promising immunotherapeutic strategy; yet, its efficacy remains limited. We evaluated FT538, a clinical-grade NK product derived from induced pluripotent stem cells (iPSCs), in glioblastoma models.</p><p><strong>Methods: </strong>FT538, engineered with a high-affinity noncleavable CD16 Fc receptor, a membrane-bound IL-15/IL-15Rα fusion protein, and CD38 knockout, was tested against 13 patient-derived glioblastoma stem-like cells (GSCs) in vitro and in orthotopic xenograft models. Intracranial persistence and neurotoxicity were assessed in mice. Surface proteomics identified therapeutic targets, and a B7-H3-targeted tri-specific killer engager (TriKE) was evaluated with FT538 and NKG2C+ adaptive NK cells.</p><p><strong>Results: </strong>Glioblastoma stem-like cells were classified as sensitive (38%), moderately sensitive (38%), or resistant (23%) to FT538. Intracranial administration in mice was well tolerated, persisted for at least 35 days, and caused no neurotoxicity. A single intratumoral dose induced complete regression in sensitive xenografts. Surface profiling identified B7-H3 as a target to overcome resistance. Combination therapy with FT538 and a B7-H3 TriKE enhanced antitumor efficacy in resistant models, an effect also observed with adaptive NK cells.</p><p><strong>Conclusions: </strong>FT538 exhibits potent tumoricidal activity in 77% of GSC lines (NK-sensitive and moderately sensitive), with curative potential in sensitive models, and demonstrates favorable persistence and tolerability in vivo. B7-H3-targeted TriKE restores NK sensitivity in resistant tumors. These findings provide a strong preclinical rationale for further clinical evaluation of FT538, alone or combined with B7-H3-targeted TriKE, for glioblastoma and other solid tumors.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2369-2383"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148422899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-grade astrocytoma with piloid features: A clinical and genomic analysis of prognostic factors using a large cohort.","authors":"Shuodan Zhang, Omkar Singh, Karen Dazelle, Martha Quezado, Patrick J Cimino, Zied Abdullaev, Jing Wu, Calixto-Hope Lucas, Karisa C Schreck, Matthias Holdhoff, Peter Pytel, Vanessa Goodwill, Rob Macaulay, William McDonald, Roberta Seidman, Matthew Wood, Krishna Bharani, Janna Neltner, Hope Richard, Koping Chang, Linda Szymanski, Stephen Yip, Abir Mukherjee, Osorio Lopes Abath Neto, Suash J Sharma, Richard Green, Daniel Brown, Maria A Gubbiotti, Leomar Y Ballester, Jennifer Eschbacher, Matthew Smith-Cohn, Murat Gokden, Cristina Vincentelli, William Yong, Julieann Lee, Christopher Mount, Joseph Fulmer, Michael Sun, Keith Ligon, Mariarita Santi, Emily Ling-Lin Pai, Gabrielle Yeaney, Sanda Alexandrescu, Ravi Raghavan, Igor Fernandes, Gerald Feliz Reis, Jacob Mandel, Dario Caccamo, Shilpa Rao, Omar H Butt, Sonika Dahiya, Sara Stone, Kyle Conway, MacLean P Nasrallah, Christine Fuller, Angus Toland, Rimas V Lukas, David Cachia, Erik J Uhlmann, Matthew McCord, Jeffrey Helgager, Karam Han, Arie Perry, Sandra Perez, Elena Daoud, Darby BeDell, Hilary Highfield, Peter Kobalka, James Stephen Nix, Edjah Nduom, Stewart Neill, Mark R Gilbert, Nelli Lakis, Adriana Fonseca, Colette Shen, Rebecca Yoda, Lenore Monterroza, Adam L Cohen, Sahara Cathcart, Md Al Amin, Jian Campian, Kenneth Aldape","doi":"10.1093/neuonc/noag145","DOIUrl":"10.1093/neuonc/noag145","url":null,"abstract":"<p><strong>Background: </strong>High-grade astrocytoma with piloid features (HGAP) is a recently defined tumor type that is not well understood. Prognostic factors of clinical outcomes are not well established.</p><p><strong>Methods: </strong>Methylation profiling was performed on tumor samples, many at the National Cancer Institute (NCI) Laboratory of Pathology, and others from publicly available sources. Methylation classifier scores of ≥0.90 to the HGAP class on the NCI-Bethesda classifier version 3 were included. Clinical features were collected from the medical record. Survival analyses were performed using the Kaplan-Meier and Cox-proportional hazards methods.</p><p><strong>Results: </strong>The cohort comprised 421 patients. There were high rates of ATRX alteration (62%), CDKN2A/B homozygous loss (78%) and MGMT promoter methylation (53%). MAPK alterations were identified in 74% of evaluable samples. The median age was 46 years, and posterior fossa location was predominant (52%). The median overall survival was 88 months. Older age (P = .01) and the presence of an ATRX alteration (P = .04) were found to be negative prognostic factors. The presence of cystic features on magnetic resonance imaging (MRI) was found to be favorably prognostic (P = .01). Factors that were not significantly associated with prognosis included histologic high-grade features, CDKN2A/B homozygous deletion, MGMT promoter methylation, extent of resection, and presence of NF1 syndrome.</p><p><strong>Conclusions: </strong>This large cohort establishes relative frequencies of several important markers. Additionally, older age, the presence of an ATRX alteration, and cystic features on MRI were found to be prognostic. Our work may aid in optimizing treatment regimens for patients with this tumor type.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2435-2448"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635591/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mature results from EORTC 22033: Implications of inferior results with monotherapy for grade 2 gliomas.","authors":"Connor J Kinslow, David Schiff","doi":"10.1093/neuonc/noag162","DOIUrl":"10.1093/neuonc/noag162","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2291-2293"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148536595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to: ΔNp73/ETS2 complex drives glioblastoma pathogenesis-targeting downstream mediators by rebastinib prolongs survival in preclinical models of glioblastoma.","authors":"","doi":"10.1093/neuonc/noag208","DOIUrl":"10.1093/neuonc/noag208","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"e35"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Durable complete response to dual immune checkpoint blockade in an MMR-deficient, Lynch syndrome-associated CNS WHO grade 3 meningioma.","authors":"Marta Maccari, Elena Marinelli, Mario Caccese, Marta Padovan, Alberto Bosio, Angela Guerriero, Luisa Bellu, Giovanni Librizzi, Sara Lonardi, Susanna Mandruzzato, Giuseppe Lombardi","doi":"10.1093/neuonc/noag239","DOIUrl":"https://doi.org/10.1093/neuonc/noag239","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112623","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":"BRAF-altered glioma in adults and children: A Society for Neuro-Oncology and European Association of Neuro-Oncology consensus review on clinical management and future directions.","authors":"Karisa C Schreck, Macarena I de la Fuente, Mary Jane Lim Fat, Sybren L N Maas, Jean M Mulcahy Levy, Giuseppe Lombardi, Sebastien Perrault, Claudia K Petritsch, Kenneth Aldape, Susan M Chang, Johnny Duerinck, Matthias Holdhoff, Tomas Kazda, Emilie Le Rhun, Giuseppe Minniti, Mark V Mishra, Sabine Mueller, Marta Padovan, Matthias Preusser, Marion Smits, Michael Weller, Patrick Y Wen, Martin van den Bent, Marjolein Geurts","doi":"10.1093/neuonc/noag135","DOIUrl":"10.1093/neuonc/noag135","url":null,"abstract":"<p><p>Oncogenic BRAF alterations occur in a subset of diffuse gliomas across WHO grades and are increasingly identified through modern molecular diagnostics. In addition to standard glioma therapies, targeted treatments are available for patients with BRAF-altered glioma, supported by variable evidence spanning randomized trials, single-arm studies, and real-world evidence. This joint consensus review from the Society for Neuro-Oncology (SNO) and the European Association of Neuro-Oncology (EANO) synthesizes current knowledge on the diagnosis and management of BRAF-altered gliomas across age groups, tumor grades, and lines of therapy. Particular emphasis is placed on expert consensus in clinical scenarios where high-quality trial evidence remains limited. The review addresses rationale testing for BRAF alterations, selection, and monitoring of targeted therapies, management of treatment-related toxicities, approaches to resistance, and priorities for future research. It aims to provide practical, evidence-based guidance for clinicians while highlighting gaps to inform prospective studies.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2313-2335"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635583/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148205722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NFAM1 organizes a lipid raft-restricted DAPP1-PLCG2 module to drive M2-like GAM polarization via Ca²⁺-NFAT1 signaling in glioma.","authors":"Yaochuan Zhang, Rongjin Chen, Yifu Song, Yibin Lin, Xu Cao, Guofeng Tian, Xiaodi Han, Lin Zong, Juanhan Yu, Li Zhang, Sheng Han","doi":"10.1093/neuonc/noag240","DOIUrl":"https://doi.org/10.1093/neuonc/noag240","url":null,"abstract":"<p><strong>Background: </strong>Glioma-associated macrophages (GAMs) promote glioma progression, but the membrane-proximal mechanisms sustaining their tumor-supportive states remain poorly defined.</p><p><strong>Methods: </strong>Bulk and single-cell transcriptomic analyses, human glioma specimens, GAM models, and orthotopic glioma models were used to define the expression and function of NFAM1. Lipid-raft fractionation, co-immunoprecipitation, proximity ligation, domain-mutant rescue, IP3 and Ca²⁺ measurements, and NFAT1 nuclear translocation assays delineated its signaling mechanism. Pharmacological, macrophage-depletion/reconstitution, and inducible genetic models evaluated its therapeutic relevance.</p><p><strong>Results: </strong>NFAM1 was enriched in monocyte-derived, M2-like GAMs and associated with higher glioma grade, IDH-wild-type status, and poor survival. NFAM1 promoted GAM migration and M2-like polarization, thereby enhancing mesenchymal plasticity of glioma stem cells (GSCs), angiogenesis, and glioma progression. Mechanistically, phosphorylated NFAM1 recruited DAPP1 and PLCG2 through ITAM-SH2-dependent interactions within lipid rafts, organizing a spatially coordinated and functionally ordered signaling module. DAPP1 acted upstream of PLCG2 to promote IP3 production, Ca²⁺ signaling, and NFAT1 nuclear translocation. Madecassoside showed ITAM-dependent cellular target engagement with NFAM1, disrupted this signaling module, suppressed tumor-supportive GAM phenotypes, reduced orthotopic tumor growth, and prolonged survival. Its antitumor activity was markedly diminished after peripheral macrophage depletion or reconstitution with NFAM1-deficient bone marrow-derived macrophages. Moreover, inducible NFAM1 knockdown in reconstituted BMDM-derived GAMs after tumor establishment reduced tumor burden and extended survival.</p><p><strong>Conclusions: </strong>NFAM1 spatially organizes lipid-raft-restricted DAPP1-PLCG2-Ca²⁺-NFAT1 signaling in monocyte-derived GAMs and represents a therapeutically targetable vulnerability in glioma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149112772","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":"Epidemiological and clinical data link depot medroxyprogesterone acetate to meningioma.","authors":"Brooke C Braman, Martha A Cady, Allison A Merz-Herrala, Alon Witztum, Zora Arum, Scarlett L Gomez, Ramin A Morshed, Javier E Villanueva-Meyer, Nancy Ann Oberheim Bush, Susan M Chang, Jennifer L Kerns, David R Raleigh","doi":"10.1093/neuonc/noag115","DOIUrl":"10.1093/neuonc/noag115","url":null,"abstract":"<p><p>Meningiomas are among the few intracranial tumors that are more common in females than males. The majority of meningiomas express progesterone receptor (PR), and differences in exposure to progestogens are thought to contribute to sex-based disparity in meningioma. Previous epidemiological and clinical data have demonstrated that multiple progestins, such as cyproterone acetate (CPA), are linked to meningioma. More recently, international epidemiological studies have found a significantly increased risk of meningioma with depot medroxyprogesterone acetate (DMPA), a widely used injectable contraceptive sold under the trade name Depo-Provera. Although the absolute risk of meningioma remains small, exposure to DMPA increases the risk of meningioma by 1.5- to 5.5-fold. DMPA-associated meningiomas are clinically significant, as the risk of craniotomy for tumor resection, not just the risk of tumor diagnosis, is elevated after DMPA exposure. These data suggest that DMPA should be avoided in individuals with a history of meningioma when alternatives are available. The risk of meningioma should be discussed with patients during DMPA counseling, and the utility of screening patients with prolonged DMPA exposure for meningiomas should be investigated. Further work is needed to elucidate the mechanisms of PR signaling in meningioma and to understand the complex interplay of tumor genomics, hormone exposure and signaling, and social and structural drivers of health that may contribute to disparities in meningioma.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2338-2351"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988572","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodological considerations in the assessment of hemizygous CDKN2A/B deletions in meningioma and IDH-mutant glioma.","authors":"Franziska M Ippen, Felix Sahm, Abigail K Suwala","doi":"10.1093/neuonc/noag159","DOIUrl":"10.1093/neuonc/noag159","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2516-2517"},"PeriodicalIF":13.1,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13635578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}