Journal of Neuro-Oncology最新文献

{"title":"Clinical progress in the development of CAR T cells to treat malignant glioma.","authors":"Eric P Grewal, Brian V Nahed, Bob S Carter, Elizabeth R Gerstner, William T Curry, Marcela V Maus, Bryan D Choi","doi":"10.1007/s11060-024-04909-7","DOIUrl":"10.1007/s11060-024-04909-7","url":null,"abstract":"<p><strong>Context: </strong>Chimeric antigen receptor (CAR) T cell therapy is an exciting modality of immunotherapy that has revolutionized the treatment of hematologic malignancies. However, translating this success to malignant gliomas such as glioblastoma (GBM) and diffuse midline glioma (DMG) remains a formidable challenge due to multiple biologic, anatomic, and immunologic factors. Despite these hurdles, a number of clinical trials deployed over the last decade have increased optimism for the potential of CAR T cell therapy in glioma treatment.</p><p><strong>Evidence synthesis: </strong>We highlight historical and ongoing clinical trials of CAR T cell therapy in glioma, with a focus on key tumor-associated antigens such as IL-13Rα2, HER2, EGFR, EGFRvIII, EphA2, GD2, and B7-H3. Early studies established proof-of-concept for antigen-specific CAR T cell targeting, yet immune evasion mechanisms such as antigen downregulation and limited CAR T cell persistence remain significant obstacles. Recent approaches, including multiantigen targeting, alternative cell sources, and innovations in delivery routes offer promising strategies to overcome these challenges.</p><p><strong>Conclusions: </strong>The rapid evolution of investigational CAR T cell therapies portends great potential for the future of glioma treatment. Future studies will need to refine antigen targeting strategies, optimize CAR T cell persistence, and integrate combinatorial approaches to fully harness the therapeutic potential of this modality and improve the therapeutic window against brain tumors.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"571-579"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient and permanent hydrocephalus following resection of brain metastases located in the posterior fossa: incidence, risk factors and the necessity of perioperative external ventricular drainage placement.","authors":"Ehab Shabo, Anna-Laura Potthoff, Thomas Zeyen, Julian P Layer, Stefan Ehrentraut, Jasmin Scorzin, Felix Lehmann, Nils Christian Lehnen, Mohammed Banat, Johannes Weller, Florian Gessler, Daniel Paech, Motaz Hamed, Valeri Borger, Alexander Radbruch, Ulrich Herrlinger, Leonie Weinhold, Hartmut Vatter, Matthias Schneider","doi":"10.1007/s11060-024-04890-1","DOIUrl":"10.1007/s11060-024-04890-1","url":null,"abstract":"<p><strong>Purpose: </strong>Prophylactic insertion of an external ventricular drainage (EVD) prior to the resection of posterior fossa metastases (PFMs) is a common approach to address postoperative transient and permanent hydrocephalus. However, predicting surgery-related hydrocephalus in the preoperative phase continues to be a challenge. This study aims to analyze the incidence, preoperatively collectable risk factors and necessity of perioperative external ventricular drainage placement after posterior fossa metastasis surgery.</p><p><strong>Methods: </strong>All patients undergoing surgery for PFMs at the authors' neuro-oncological center between 2015 and 2021 were identified and assessed for postoperative hydrocephalus occurrence. Tumour volume, edema volume, and 4th ventricle volume were assessed on preoperative magnetic resonance imaging scans using the IntelliSpace Portal 5.0. A multivariable logistic regression analysis was performed to identify possible predictors for postoperative hydrocephalus occurrence.</p><p><strong>Results: </strong>Postoperative hydrocephalus occurred in 14 of the 130 identified PFM patients (11%). Multivariable analysis and receiver operating characteristic (ROC) analysis revealed a 4th -ventricle-to-tumor-volume ratio ≤ 0.02 (OR 33.1, 95% CI 3.8-284.3, p = 0.001), an edema-to- tumor-volume ratio ≤ 0.85 (OR 10.6, 95% CI 2.4-47.4, p = 0.002), an imaging-morphological contact to the 4th ventricle (OR 5, 95% CI 1.4-18, p = 0.013), and multiple intracranial metastases (OR 2.4, 95% CI 1-5.9, p = 0.045) as independent predictors for surgery-related postoperative hydrocephalus occurrence.</p><p><strong>Conclusion: </strong>The present study identifies preoperatively detectable risk factors for the occurrence of postoperative hydrocephalus following surgery for PFMs. These findings may provide guidance in clinical decision-making regarding prophylactic EVD placement.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"681-689"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cabergoline-induced NDFIP1 upregulation in pituitary neuroendocrine tumor cells activates mTOR signaling and contributes to cabergoline resistance.","authors":"Weiting Gu, Weifeng Zhang, Zhebao Wu, Yu Cai","doi":"10.1007/s11060-025-04949-7","DOIUrl":"https://doi.org/10.1007/s11060-025-04949-7","url":null,"abstract":"<p><strong>Purpose: </strong>To investigate the molecular mechanisms underlying resistance to dopamine agonists (DA).</p><p><strong>Methods: </strong>LC-MS/MS analysis was performed on rat pituitary neuroendocrine tumors (PitNET) cell line GH3 to identify differentially expressed proteins induced by cabergoline (CAB) treatment. A total of 180 human PITNET samples were subjected to transcriptome analysis. Immunohistochemistry (IHC) was conducted on 29 tumor samples to validate NDFIP1 alteration. A xenograft mouse model was established by subcutaneously injecting GH3 cells, with or without NDFIP1 overexpression, into nude mice to investigate tumor growth. PitNET cell lines were treated with CAB. Cell proliferation was assessed using the CCK-8, and protein expression levels were examined through Western blot analysis.</p><p><strong>Results: </strong>CAB treatment upregulated FDFT1 and NDFIP1 protein expression in GH3 cells, with NDFIP1 showing a significant positive correlation with tumor size, as confirmed by IHC results. MMQ and GH3 cells overexpressing NDFIP1 exhibited enhanced viability and reduced sensitivity to CAB. In vivo experiments demonstrated that subcutaneous injection of NDFIP1-overexpressing GH3 cells led to enhanced tumor growth compared to parental GH3 cells. Although the total levels of PTEN remained unaltered, NDFIP1 overexpression induced PTEN nuclear translocation, potentially activating the mTOR pathway. This was supported by increased phosphorylation of key mTOR pathway components, including p-AKT and p-4EBP1, in cells overexpressing NDFIP1.</p><p><strong>Conclusion: </strong>CAB treatment induces the upregulation of NDFIP1 in PitNET cells, which correlates with tumor size and contributes to reduced CAB sensitivity, potentially through activation of the mTOR pathway. NDFIP1 as a potential therapeutic target for overcoming DA resistance in PitNET patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143074869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implications of molecular classifications in glioma surgery.","authors":"Anita L Kalluri, Joyce H Lee, Calixto-Hope G Lucas, Jordina Rincon-Torroella, Chetan Bettegowda","doi":"10.1007/s11060-024-04883-0","DOIUrl":"10.1007/s11060-024-04883-0","url":null,"abstract":"<p><strong>Purpose: </strong>The incorporation of molecular markers into neuro-oncology has transformed our understanding of adult diffuse gliomas. While surgical resection is the mainstay of treatment for many patients with gliomas, surgical management strategies warrant re-exploration in the context of characteristic molecular profiles.</p><p><strong>Methods: </strong>We reviewed the neurosurgical and neuro-oncological literature for studies investigating surgery in molecularly defined cohorts of adult diffuse gliomas.</p><p><strong>Results: </strong>We discuss key molecular markers associated with the three subtypes of adult diffuse glioma: glioblastoma IDH-wildtype, astrocytoma IDH-mutant, and oligodendroglioma IDH-mutant and 1p/19q codeleted. We additionally discuss surgical strategies and extent of resection in these tumors, framing them in the context of key molecular alterations. Finally, we briefly discuss the practical utility of molecular markers in guiding surgical decision making.</p><p><strong>Conclusion: </strong>Molecular markers in gliomas are of growing relevance to surgical intervention. Advancements in preoperative and intraoperative molecular diagnostics will increase the utility of molecular biomarkers in informing surgical decision-making for patients with gliomas.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"559-569"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CAR-engineered NK cells versus CAR T cells in treatment of glioblastoma; strength and flaws.","authors":"Mohammadmahdi Sabahi, Ali Fathi Jouzdani, Zohre Sadeghian, Mohammad Amin Dabbagh Ohadi, Hadi Sultan, Arash Salehipour, Lana Maniakhina, Nima Rezaei, Badih Adada, Alireza Mansouri, Hamid Borghei-Razavi","doi":"10.1007/s11060-024-04876-z","DOIUrl":"10.1007/s11060-024-04876-z","url":null,"abstract":"<p><p>Glioblastoma (GBM) is a highly aggressive primary brain tumor that carries a grim prognosis. Because of the dearth of treatment options available for treatment of GBM, Chimeric Antigen Receptor (CAR)-engineered T cell and Natural Killer (NK) therapy could provide alternative strategies to address the challenges in GBM treatment. In these approaches, CAR T and NK cells are engineered for cancer-specific immunotherapy by recognizing surface antigens independently of major histocompatibility complex (MHC) molecules. However, the efficacy of CAR T cells is hindered by GBM's downregulation of its targeted antigens. CAR NK cells face similar challenges, but, in contrast, they offer advantages as off-the-shelf allogeneic products, devoid of graft-versus-host disease (GVHD) risk as well as anti-cancer activity beyond CAR specificity, potentially reducing the risk of relapse or resistance. Despite CAR T cell therapies being extensively studied in clinical settings, the use of CAR-modified NK cells in GBM treatment remains largely in the preclinical stage. This review aims to discuss recent advancements in NK cell and CAR T cell therapies for GBM, including methods for introducing CARs into both NK cells and T cells, addressing manufacturing challenges, and providing evidence supporting the efficacy of these approaches from preclinical and early-phase clinical studies. The comprehensive evaluation of CAR-engineered NK cells and CAR T cells seeks to identify the optimal therapeutic approach for GBM, contributing to the development of effective immunotherapies for this devastating disease.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"495-530"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patient-derived glioma organoids real time identification of IDH mutation, 1p/19q-codeletion and CDKN2A/B homozygous deletion with differential ion mobility spectrometry.","authors":"Ismaïl Hermelo, Ilkka Haapala, Meri Mäkelä, Dafne Jacome Sanz, Anton Kontunen, Markus Karjalainen, Philipp Müller, Kai Lehtimäki, Matti Nykter, Juhana Frösén, Hannu Haapasalo, Antti Roine, Niku Oksala, Kristiina Nordfors, Antti Vehkaoja, Joonas Haapasalo","doi":"10.1007/s11060-024-04891-0","DOIUrl":"10.1007/s11060-024-04891-0","url":null,"abstract":"<p><strong>Purpose: </strong>Extent of brain tumor resection continues to be one of the central decisions taken during standard of care in glioma patients. Here, we aimed to evaluate the most essential molecular factors, such as IDH (isocitrate dehydrogenase) mutation in gliomas classification with patient-derived glioma organoids (PGOs) using differential mobility spectrometry (DMS).</p><p><strong>Methods: </strong>we prospectively recruited 12 glioma patients, 6 IDH-mutated and 6 IDH wild-type tumors, from which PGOs were generated ex-vivo. Altogether, 320 PGOs DMS spectra were analyzed with a classifier algorithm based on linear discriminant analysis (LDA).</p><p><strong>Results: </strong>LDA model classification accuracy (CA) obtained between IDH-mutant and IDH wild-type PGOs was 90% (91% sensitivity and 89% specificity). Furthermore, 1p/19q codeletion classification within IDH mutant PGOs reached 98% CA (93% sensitivity and 99% specificity), while CDKN2A/B homozygous loss status had 86% CA (63% sensitivity 93% specificity).</p><p><strong>Conclusion: </strong>DMS suitability to differentiate IDH-mutated PGOs was thus validated in ex vivo cultured samples, PGOs. Preliminary results regarding 1p/19q codeleted PGOs and CDKN2A/B loss PGOs identification endorse testing in a prospective intraoperative glioma patient cohort. Our results reveal a sample classification set-up that is compatible with real-time intraoperative surgery guidance.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"691-703"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729090/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693172","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in intraoperative therapies in neurosurgical oncology: a narrative review.","authors":"Benjamin Rodriguez, Daniel Rivera, Jack Y Zhang, Cole Brown, Tirone Young, Tyree Williams, Justiss Kallos, Sakibul Huq, Constantinos Hadjpanayis","doi":"10.1007/s11060-024-04882-1","DOIUrl":"10.1007/s11060-024-04882-1","url":null,"abstract":"<p><strong>Purpose: </strong>High-grade gliomas (HGG) represent the most aggressive primary brain tumors in adults, characterized by high recurrence rates due to incomplete resection. This review explores the effectiveness of emerging intraoperative therapies that may extend survival by targeting residual tumor cells. The main research question addressed is: What recent intraoperative techniques show promise for complementing surgical resection in HGG treatment?</p><p><strong>Methods: </strong>A comprehensive literature review was conducted, examining recent studies on intraoperative therapeutic modalities that support surgical resection of HGG. Techniques reviewed include laser interstitial thermal therapy (LITT), intraoperative brachytherapy, photodynamic therapy (PDT), sonodynamic therapy (SDT), and focused ultrasound (FUS). Each modality was evaluated based on clinical application, evidence of effectiveness, and potential for integration into standard HGG treatment protocols.</p><p><strong>Results: </strong>Findings indicate that these therapies offer distinct mechanisms to target residual tumor cells: LITT provides localized thermal ablation; intraoperative brachytherapy delivers sustained radiation; PDT and SDT activate cytotoxic agents in tumor cells; and FUS enables precise energy delivery. Each method has shown varying levels of clinical success, with PDT and LITT currently more widely implemented, while SDT and FUS are promising but under investigation.</p><p><strong>Conclusion: </strong>Intraoperative therapies hold potential to improve surgical outcomes for HGG by reducing residual tumor burden. While further clinical studies are needed to optimize these techniques, early evidence supports their potential to enhance the effectiveness of surgical resection and improve patient survival in HGG management.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"549-557"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The 5-factor modified frailty index as a prognostic factor for stereotactic radiosurgery in meningioma management.","authors":"Sanjeev Herr, Trent Kite, Praveer Vyas, Stephen Karlovits, Alexander Yu, Rodney E Wegner, Matthew J Shepard","doi":"10.1007/s11060-024-04873-2","DOIUrl":"10.1007/s11060-024-04873-2","url":null,"abstract":"<p><strong>Purpose: </strong>Meningiomas are the most frequent primary intracranial malignancy. While surgical resection can confer long term tumor control, stereotactic radiosurgery (SRS) is often used for small, asymptomatic tumors in the adjuvant setting. Frailty has been associated with increased rates of peri-operative morbidity but has yet to be defined in the setting of SRS for meningiomas. We therefore sought to examine the relationship between frailty and clinical/radiographic outcomes of patients with meningiomas who have undergone SRS.</p><p><strong>Methods: </strong>A single-center, retrospective cohort study classified patients by their 5-factor modified frailty index (mFI-5) score into pre-frail (0-1) and frail (2-5) at the time of SRS treatment. Evaluations of overall survival (OS), progression free survival (PFS), local control (LC), and distant control (DC) were performed using Kaplan-Meier analysis. Cox proportional hazards regression analysis was used to further define factors associated with OS/PFS.</p><p><strong>Results: </strong>94 patients met inclusion criteria and underwent SRS for meningioma treatment from 2019 to 2023. Analyses compared prefrail (0-1) and frail (2-5) individuals. Kaplan-Meier analysis demonstrated a near significant association between frailty and OS (HR 3.66, 95% CI 0.49-26.8 p = 0.05) with 3-year OS rates of 75.4% in the pre-frail versus 36.6% in the frail group. However, a significant relationship was demonstrated between frailty and PFS (HR: 2.95 95% CI 1.12-7.81, p = 0.02) with 3-year PFS rates of 90.5% in the pre-frail group versus 49.2% in the frail group. Univariable regression analysis demonstrated that frailty, prior surgical excision, and cumulative tumor volume predicted PFS.</p><p><strong>Conclusion: </strong>Frailty, as assessed by the mFI-5, did not independently predict OS but did predict PFS in individuals with meningioma undergoing SRS.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"581-588"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142622176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The clinical impact of EGFR alterations in elderly glioblastoma patients: results from a real-life cohort.","authors":"Séréna Pulcini, Ludivine Beaussire-Trouvay, Florent Marguet, Pierre-Julien Viailly, Olivier Langlois, Cristina Alexandru, Isabelle Tennevet, Fréderic Di Fiore, Nasrin Sarafan-Vasseur, Maxime Fontanilles","doi":"10.1007/s11060-024-04879-w","DOIUrl":"10.1007/s11060-024-04879-w","url":null,"abstract":"<p><strong>Background: </strong>The incidence of glioblastoma in the elderly population is increasing as the worldwide population ages. The differential and poorer survival in the elderly population compared to younger patients is partially explained. The present study aimed to investigate the clinical impact of epidermal growth factor receptor EGFR-altered glioblastoma in a real-life elderly glioblastoma population.</p><p><strong>Patients and methods: </strong>A bicentric and retrospective study was conducted. Patients were 70 years or older and suffering from histomolecularly confirmed glioblastoma. Single nucleotide variants (SNV), amplification, or chromosome 7 polysomy were sought. The primary endpoint was the comparison of overall survival (OS) in patients with or without EGFR alteration. Secondary objectives were to determine other clinical parameters correlated with EGFR alteration status.</p><p><strong>Results: </strong>Seventy-three patients were analyzed: 41.1% had at least one EGFR alteration. The presence of EGFR alteration did not impact overall survival: HR 0.97 [0.6-1.57], p = 0.9; the median overall survival was 6.5 months [5.3-9.3] in the EGFR-altered group versus 7 months [4.5-10] in the EGFR wild-type group, p = 0.75. In multivariate analysis, tumor resection was associated with a significant overall survival improvement: the median OS in the resected group (n = 20) was 11 months [95% CI 7.8-22] versus a median OS of 5.5 months [4.6-7.8] in the unresected group (n = 53), without correlation to EGFR alteration status.</p><p><strong>Conclusion: </strong>In the modern era of molecular characterization and improved treatment modalities, the presence of at least one EGFR alteration did not influence survival outcomes in an elderly population of glioblastoma patients.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"619-628"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142644445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"BRD4 promotes immune escape of glioma cells by upregulating PD-L1 expression.","authors":"Yongsheng Liu, Lize Cai, Hao Wang, Lin Yao, Yue Wu, Kai Zhang, Zuopeng Su, Youxin Zhou","doi":"10.1007/s11060-024-04889-8","DOIUrl":"10.1007/s11060-024-04889-8","url":null,"abstract":"<p><strong>Purpose: </strong>Glioblastoma multiforme (GBM) poses significant challenges in treatment due to its aggressive nature and immune escape mechanisms. Despite recent advances in immune checkpoint blockade therapies, GBM prognosis remains poor. The role of bromodomain and extraterminal domain (BET) protein BRD4 in GBM, especially its interaction with immune checkpoints, is not well understood. Our study aimed to explore the role of BRD4 in GBM, especially the immune aspects.</p><p><strong>Methods: </strong>In this study, we performed bioinformatics gene expression and survival analysis of BRD4 using TCGA and CGGA databases. In addition, we investigated the effects of BRD4 on glioma cell proliferation, invasion and migration by clone formation assay, Transwell assay, CCK8 assay and wound healing assay. Chromatin immunoprecipitation (ChIP) assay was conducted to confirm BRD4 binding to the programmed death ligand 1 (PD-L1) promoter. GL261 cells with BRD4 shRNA and/or PD-L1 cDNA were intracranially injected into mice to investigate tumor growth and survival time. Tumor tissue characteristics were analyzed using H&E and IHC staining and immune cell infiltration were assessed by flow cytometry.</p><p><strong>Results: </strong>The results showed that elevated expression of BRD4 in high-grade gliomas was associated with poor patient survival. In addition, we validated the promotional effects of BRD4 on glioma cell proliferation, invasion and migration. The results of ChIP experiments showed that BRD4 is a regulator of PD-L1 at the transcriptional level, implying that it is involved in the immune escape mechanism of glioma cells. In vivo studies showed that BRD4 knockdown inhibited tumor growth and reduced immunosuppression, improving prognosis.</p><p><strong>Conclusion: </strong>BRD4 has the capability to regulate the growth of glioblastoma and enhance immune suppression by promoting PD-L1 expression. Targeting BRD4 represents a promising direction for future research and treatment.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"669-679"},"PeriodicalIF":3.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739672","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}