Impact of corticosteroid administration on contrast-enhancing volume and diffusion MRI in treatment naïve glioblastoma

皮质类固醇给药对初治胶质母细胞瘤强化体积及扩散磁共振成像的影响

Corticosteroids impact the radiographic interpretation of glioblastoma, including artificial reduction in contrast-enhancing tumor volume and intensity (i.e., a "pseudoresponse") and in the apparent coefficient diffusion (ADC). This study aimed to estimate the influence of corticosteroids on these measurements in treatment naïve glioblastoma before surgery. Corticosteroid administration can induce a significant "pseudoresponse" in glioblastoma, with an observed reduction in contrast-enhancing tumor volume of 23.7% and a time interval adjusted reduction of 44.0% (25.7-62.2%), and an ADC drop of 180×10-6 mm2/s (14.2%). These data confirm that radiographic measurements are impacted by corticosteroids and provide benchmarks for development of adjusted response criteria accounting for corticosteroid use.

皮质类固醇会影响胶质母细胞瘤的影像学解读，包括人为降低肿瘤强化体积和强化程度（即“假性反应”）以及表观扩散系数（ADC）。本研究旨在评估皮质类固醇对手术前初治胶质母细胞瘤这些测量指标的影响。使用皮质类固醇可在胶质母细胞瘤中诱发显著的“假性反应”，观察到强化肿瘤体积减少了23.7%，经时间间隔调整后减少了44.0%（25.7 - 62.2%），ADC下降了180×10⁻⁶mm²/s（14.2%）。这些数据证实影像学测量指标会受到皮质类固醇的影响，并为制定考虑皮质类固醇使用情况的调整后疗效评估标准提供了参考。

REF: Sanvito F, Kim A, Raymond C, et al. Impact of corticosteroid administration on contrast-enhancing volume and diffusion MRI in treatment naïve glioblastoma. Neuro Oncol. Published online May 30, 2025. doi:10.1093/neuonc/noaf136 PMID: 40443040

Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4

新诊断的异柠檬酸脱氢酶（IDH）突变型世界卫生组织（WHO）4级星形细胞瘤预后的临床、分子和影像学预测因素

Astrocytoma, isocitrate dehydrogenase-mutant, WHO grade 4 (Astro4), is a new tumor type in the 2021 WHO classification of central nervous system tumors that has been poorly characterized in the literature. This study evaluates predictors of prognosis in a large cohort of newly diagnosed Astro4. Our study comprehensively characterizes a large cohort of newly diagnosed patients with Astro4, emphasizing the prognostic value of CDKN2A/B deletion, age, and the extent of resection of enhancing disease in these patients.

异柠檬酸脱氢酶突变型、WHO 4 级星形细胞瘤（Astro4）是 2021 年世界卫生组织中枢神经系统肿瘤分类中的一种新肿瘤类型，相关文献对其描述较少。本研究评估了一大群新诊断的 Astro4 患者的预后预测因素。我们的研究全面描绘了一大群新诊断的 Astro4 患者的特征，强调了 CDKN2A/B 缺失、年龄以及强化病灶切除范围对这些患者的预后价值。

REF: Lasica AB, Lan Z, Miller JJ, et al. Clinical, molecular and radiological predictors of prognosis in newly diagnosed astrocytoma, IDH-mutant, WHO grade 4. Neuro Oncol. Published online May 29, 2025. doi:10.1093/neuonc/noaf133 PMID: 40440464

Glioblastoma-enriched glycosphingolipids modulate the function of human iNKT cells

胶质母细胞瘤富集的糖鞘脂调节人类恒定自然杀伤性T细胞的功能

To develop effective therapies for glioblastoma (GBM), a deeper understanding of its underlying immunoregulatory mechanisms is needed. Invariant natural killer T (iNKT) cells are unconventional T cells that recognize lipid antigens and are known to regulate tumor immunity in other cancer types. Given the lipid-rich nature of the brain and the unique metabolic activity of GBM cells, we hypothesized that GBM-enriched lipids could direct iNKT cells to contribute to the immunosuppressive nature of the disease. The modulation of iNKT cell functions by GSC-enriched glycosphingolipids may contribute to the immunosuppression of GBM and highlights sulfatide production as a potential therapeutic target for GBM treatment.

为了开发有效的胶质母细胞瘤（GBM）治疗方法，需要更深入地了解其潜在的免疫调节机制。恒定自然杀伤T（iNKT）细胞是一类非常规T细胞，能识别脂质抗原，且已知其可调节其他癌症类型的肿瘤免疫。鉴于大脑富含脂质的特性以及GBM细胞独特的代谢活性，我们推测GBM中富集的脂质可能引导iNKT细胞参与该疾病的免疫抑制特性。神经胶质瘤干细胞（GSC）富集的糖鞘脂对iNKT细胞功能的调节可能导致GBM的免疫抑制，并凸显了硫酸脑苷脂的产生作为GBM治疗潜在靶点的可能性。

REF: Coombs MJ, Dowdy T, Alam MM, et al. Glioblastoma-enriched glycosphingolipids modulate the function of human iNKT cells. Neuro Oncol. Published online May 28, 2025. doi:10.1093/neuonc/noaf135 PMID: 40435375

A Clinically Annotated Transcriptomic Atlas of Nervous System Tumors

神经系统肿瘤的临床注释转录组图谱

While DNA methylation signatures are distinct across nervous system neoplasms, it has not been comprehensively demonstrated whether transcriptomic signatures exhibit similar uniqueness. Additionally, no large-scale dataset for comparative gene expression analyses exists. This study addresses these knowledge and resource gaps. Like bulk DNA methylation, we demonstrate that bulk transcriptomic signatures are distinct across the diagnostic spectrum of nervous system neoplasms. Our atlas' broad coverage of diagnoses, including rarely studied entities, spans all ages and includes individuals from diverse geographical regions, enhancing its utility for comprehensive and robust comparative gene expression analyses, as exemplified by our PH/PG analyses. For access visit http://kdph.shinyapps.io/atlas/ or https://github.com/axitamm/BrainTumorAtlas.

虽然神经系统肿瘤的DNA甲基化特征各不相同，但转录组特征是否也具有类似的独特性尚未得到全面证实。此外，目前还没有用于比较基因表达分析的大规模数据集。本研究填补了这些知识和资源方面的空白。我们发现，与整体DNA甲基化一样，神经系统肿瘤在整个诊断范围内的整体转录组特征也具有独特性。我们的图谱广泛涵盖了各类诊断，包括很少被研究的肿瘤类型，涵盖所有年龄段，并纳入了来自不同地理区域的个体，这增强了其在进行全面且可靠的比较基因表达分析中的实用性，我们对毛细胞型星形细胞瘤/毛黏液样型星形细胞瘤的分析就体现了这一点。如需访问，请登录http://kdph.shinyapps.io/atlas/ 或https://github.com/axitamm/BrainTumorAtlas。

REF: Le CH, Nelson AK, Berrones AJ, et al. A Clinically Annotated Transcriptomic Atlas of Nervous System Tumors. Neuro Oncol. Published online May 27, 2025. doi:10.1093/neuonc/noaf130 PMID: 40423244

Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma

多胺乙酰化介导癌细胞与髓系细胞之间的串扰，以促进胶质母细胞瘤中的间充质/多代谢状态

Metabolic reprogramming in glioblastoma (GBM) is a putative determinant of GBM subtype, malignant cell state and tumor-immune crosstalk. In the present study, we investigated how polyamine metabolic rewiring contributes to the malignant cell-intrinsic and microenvironment-dependent biological processes underpinning GBM subtype classification. Collectively, the findings highlight a previously unidentified role for SAT1 and its product, N1-acetylspermidine, in bridging the metabolic activity of tumor cells and tumor-associated macrophages/myeloid cells (TAMs), together promoting mesenchymal/plurimetabolic states and therapeutic resistance in GBM.

胶质母细胞瘤（GBM）的代谢重编程是GBM亚型、恶性细胞状态和肿瘤 - 免疫串扰的一个假定决定因素。在本研究中，我们探究了多胺代谢重布线如何促成支撑GBM亚型分类的恶性细胞内在和依赖微环境的生物学过程。总体而言，这些发现凸显了精胺/亚精胺N1 - 乙酰转移酶1（SAT1）及其产物N1 - 乙酰亚精胺在连接肿瘤细胞和肿瘤相关巨噬细胞/髓样细胞（TAMs）的代谢活动方面的一个此前未被发现的作用，二者共同促进GBM的间充质/多代谢状态和治疗抗性。

REF: Rana AB, Horton TM, Thakur VS, et al. Polyamine acetylation mediates crosstalk between cancer cells and myeloid cells to promote mesenchymal/plurimetabolic states in glioblastoma. Neuro Oncol. Published online May 27, 2025. doi:10.1093/neuonc/noaf128 PMID: 40424600

Postoperative radiotherapy in subtotally-resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles

具有中/高危分子特征的世界卫生组织1级次全切除复发脑膜瘤的术后放疗

Meningiomas represent the most common primary intracranial tumors in adults, with WHO grade 1 typically associated with favorable outcomes following gross total resection (GTR). Our findings highlight the combined impact of both the extent of resection (EoR) and molecular risk profile on prognosis in newly diagnosed cases. While conservative management is feasible in lower-risk primary cases, recurrent or higher-risk patients may benefit from early postoperative RT.

脑膜瘤是成人最常见的原发性颅内肿瘤，世界卫生组织（WHO）1级脑膜瘤在全切除（GTR）后通常预后良好。我们的研究结果强调了切除范围（EoR）和分子风险特征对新诊断病例预后的综合影响。对于低风险的原发性病例，保守治疗是可行的，而复发或高风险患者可能从术后早期放疗中获益。

REF: Deng MY, Maas SLN, Anil G, et al. Postoperative radiotherapy in subtotally-resected recurrent WHO grade 1 meningiomas with intermediate-/high-risk molecular profiles. Neuro Oncol. Published online May 27, 2025. doi:10.1093/neuonc/noaf125 PMID: 40424588

Transient mRNA CAR T cells targeting GD2 provide dose-adjusted efficacy against diffuse midline glioma and high grade glioma models

靶向GD2的瞬时mRNA嵌合抗原受体（CAR）T细胞对弥漫性中线胶质瘤和高级别胶质瘤模型具有可调节剂量的疗效

Diffuse midline glioma (DMG) and high grade glioma are devastating pediatric central nervous system tumors that remain incurable. Recent chimeric antigen receptor (CAR) T cell studies have shown proof of concept and early signs of efficacy against DMG targeting GD2. Prior work and ongoing clinical trials have focused on using viral vectors to create permanent CAR T cells. However, virally transduced GD2-directed CAR T cells have shown significant neurotoxicity in both pre-clinical models and human trials. Our results demonstrate the utility of transient mRNA CAR T cells delivered intratumorally to provide effective tumor killing with a defined half-life, allowing for modulation of the dose and potential side effects. We anticipate this study will expand the use of CAR T cell therapy for DMG and other central nervous system tumors and non-malignant disorders, where concern for toxicity from permanently expressing CAR T cells may hinder development.

弥漫性中线胶质瘤（DMG）和高级别胶质瘤是极具破坏性的儿童中枢神经系统肿瘤，目前仍无法治愈。近期的嵌合抗原受体（CAR）T细胞研究已证实了针对GD2治疗DMG的概念验证，并显示出早期疗效迹象。此前的研究和正在进行的临床试验都集中于使用病毒载体来制备永久性CAR T细胞。然而，经病毒转导的GD2定向CAR T细胞在临床前模型和人体试验中均显示出显著的神经毒性。我们的研究结果证明了瘤内注射瞬时mRNA CAR T细胞的实用性，这些细胞能有效杀伤肿瘤，且半衰期明确，从而可以调节剂量和潜在的副作用。我们预计这项研究将拓展CAR T细胞疗法在DMG及其他中枢神经系统肿瘤和非恶性疾病中的应用，因为在这些情况下，对永久性表达CAR T细胞毒性的担忧可能会阻碍其发展。

REF: Foster JB, Madsen PJ, Harvey K, et al. Transient mRNA CAR T cells targeting GD2 provide dose-adjusted efficacy against diffuse midline glioma and high grade glioma models. Neuro Oncol. Published online May 24, 2025. doi:10.1093/neuonc/noaf115 PMID: 40411488

Tumor-associated macrophage-derived exosomes modulate the immunotherapeutic sensitivity of SHH-medulloblastoma by targeting m6A-modified FOXD1

肿瘤相关巨噬细胞来源的外泌体通过靶向 m6A 修饰的 FOXD1 调节 Sonic Hedgehog（SHH）型髓母细胞瘤的免疫治疗敏感性

Medulloblastoma (MB) is the most common pediatric malignant brain tumor. Infiltration of tumor-associated macrophages (TAMs) and m6A modification of RNA are correlated with poor prognosis and tumor progression in the Sonic Hedgehog (SHH) subtype (SHH-MB). However, the relationship between TAMs infiltration in SHH-MB and m6A modification status during tumor progression remains unclear. Our study revealed for the first time that TAM-derived exosomes modulate m6A levels in SHH-MB, which promotes tumor progression via FOXD1. We identified FOXD1 as a novel therapeutic target whose inhibition sensitizes SHH-MB to immune checkpoint blockade.

髓母细胞瘤（MB）是最常见的儿童恶性脑肿瘤。肿瘤相关巨噬细胞（TAMs）浸润和RNA的m6A修饰与 Sonic Hedgehog（SHH）亚型（SHH - MB）的预后不良和肿瘤进展相关。然而，在肿瘤进展过程中，SHH - MB中TAMs浸润与m6A修饰状态之间的关系仍不清楚。我们的研究首次揭示，TAM来源的外泌体可调节SHH - MB中的m6A水平，通过FOXD1促进肿瘤进展。我们确定FOXD1是一个新的治疗靶点，抑制该靶点可使SHH - MB对免疫检查点阻断治疗更敏感。

REF: Liu Y, Peng Y, Song C, et al. Tumor-associated macrophage-derived exosomes modulate the immunotherapeutic sensitivity of SHH-medulloblastoma by targeting m6A-modified FOXD1. Neuro Oncol. Published online May 22, 2025. doi:10.1093/neuonc/noaf123 PMID: 40401803

ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis

罗宾：一种基于纳米孔的统一检测方法，集成术中甲基化组分类和次日综合分析，用于超快速肿瘤诊断

Advances in our technological capacity to interrogate CNS tumor biology have led to the ever increasing use of genomic sequencing in diagnostic decision making. Presently, CNS tumors are classified based on their epigenetic signatures, leading to a paradigm shift in diagnostic pathways. Such testing can be performed so rapidly using nanopore sequencing that results can be provided intraoperatively. This information greatly improves the fidelity of smear diagnosis and can help surgeons tailor their approach, balancing the risks of surgery with the likely benefit. Nevertheless, full integrated diagnosis may require subsequent additional assays to detect pathognomonic somatic mutations and structural variants, thereby delaying the time to final diagnosis. Nanopore sequencing can greatly improve turnaround times for standard-of-care diagnostic testing and is furthermore able to reliably provide clinically actionable intraoperative tumor classification.

我们在探究中枢神经系统（CNS）肿瘤生物学方面的技术能力取得了进展，这使得基因组测序在诊断决策中的应用日益广泛。目前，中枢神经系统肿瘤是根据其表观遗传学特征进行分类的，这导致了诊断途径的范式转变。利用纳米孔测序技术进行此类检测速度极快，术中即可得出结果。这些信息能极大提高涂片诊断的准确性，还能帮助外科医生调整手术方案，在手术风险和可能的益处之间取得平衡。然而，全面的综合诊断可能需要后续进行额外检测，以发现具有诊断意义的体细胞突变和结构变异，从而延迟最终诊断时间。纳米孔测序能显著缩短标准诊断检测的周转时间，而且还能在术中可靠地提供具有临床指导意义的肿瘤分类结果。

REF: Deacon S, Cahyani I, Holmes N, et al. ROBIN: A unified nanopore-based assay integrating intraoperative methylome classification and next-day comprehensive profiling for ultra-rapid tumor diagnosis. Neuro Oncol. Published online May 20, 2025. doi:10.1093/neuonc/noaf103 PMID: 40392954