Mesothelin is a surface antigen present on human meningioma and can be effectively targeted by CAR T-cellsGet accessArrow

间皮素是一种存在于人类脑膜瘤表面的抗原，可被嵌合抗原受体（CAR）T细胞有效靶向。获取通道 箭头（注：“Get accessArrow”这里不太明确“Arrow”的准确含义，可结合具体语境进一步确认）

Meningioma is the most common primary CNS tumor, with high-grade cases exhibiting aggressive behavior, frequent recurrence, and poor prognosis. Currently, no systemic therapies are approved for recurrent or malignant meningiomas. Chimeric antigen receptor (CAR) T-cell therapy has shown efficacy in hematologic malignancies and promise for solid tumors but its use for meningiomas has been underexplored. Mesothelin, a glycoprotein overexpressed in several solid tumors of mesodermal origin, may serve as a viable immunotherapeutic target. This study aimed to evaluate mesothelin as a CAR T-cell target in meningiomas. Mesothelin is a viable CAR T-cell target for meningiomas, and mesothelin-specific CAR T-cell therapy shows strong preclinical efficacy. These findings provide a rationale for early-phase clinical trials of mesothelin CAR T-cell therapy in patients with refractory meningiomas.

脑膜瘤是最常见的原发性中枢神经系统肿瘤，高级别病例表现出侵袭性、频繁复发和预后不良的特点。目前，尚无全身性疗法获批用于复发性或恶性脑膜瘤。嵌合抗原受体（CAR）T细胞疗法已在血液系统恶性肿瘤中显示出疗效，且对实体瘤也有应用前景，但在脑膜瘤中的应用研究尚不充分。间皮素是一种在多种中胚层来源的实体瘤中过表达的糖蛋白，可能是一种可行的免疫治疗靶点。本研究旨在评估间皮素作为脑膜瘤CAR T细胞治疗靶点的可行性。间皮素是脑膜瘤可行的CAR T细胞治疗靶点，间皮素特异性CAR T细胞疗法在临床前研究中显示出强大的疗效。这些发现为在难治性脑膜瘤患者中开展间皮素CAR T细胞疗法的早期临床试验提供了理论依据。

REF: Ramapriyan R, Barker FG 2nd, Richardson LG, et al. Mesothelin is a surface antigen present on human meningioma and can be effectively targeted by CAR T-cells. Neuro Oncol. Published online June 28, 2025. doi:10.1093/neuonc/noaf155 PMID: 40579924

Final Report on NCCTG N0877 (Alliance): A Phase II Randomized, Placebo-Controlled Trial of Chemoradiotherapy with or without Dasatinib for Glioblastoma

北中部癌症治疗组N0877（联盟）最终报告：一项关于多形性胶质母细胞瘤接受或不接受达沙替尼同步放化疗的随机、安慰剂对照Ⅱ期试验

Dasatinib is an oral inhibitor of the Src kinase family, with preclinical data indicating impact on gliomagenesis, tumor invasion, and radiosensitivity. The addition of dasatinib to standard chemoradiation did not improve outcomes for patients with glioblastoma.

达沙替尼是一种口服的Src激酶家族抑制剂，临床前数据显示其对胶质细胞瘤发生、肿瘤侵袭和放射敏感性有影响。在标准放化疗基础上加用达沙替尼并不能改善胶质母细胞瘤患者的预后。

REF: Breen WG, Dixon JG, Anderson SK, et al. Final Report on NCCTG N0877 (Alliance): A Phase II Randomized, Placebo-Controlled Trial of Chemoradiotherapy with or without Dasatinib for Glioblastoma. Neuro Oncol. Published online June 28, 2025. doi:10.1093/neuonc/noaf156 PMID: 40579995

Assessing time-trend bias in glioblastoma prognosis over two decades of clinical trialsGet accessArrow

评估二十多年临床试验中胶质母细胞瘤预后的时间趋势偏倚 获取权限 箭头（注：“箭头”可能需要结合更具体语境准确理解，这里直接按字面翻译）

The time-trend bias represents a potential limitation in the use of external controls in glioblastoma (GBM) trials. In this study, we assessed whether outcomes for newly diagnosed GBM (ndGBM) patients treated with the standard Stupp protocol in clinical trials have changed over the past two decades. No evidence of time-trend bias was observed in Phase 3 GBM trials over the past two decades once major prognostic factors were accounted for.

时间趋势偏倚是胶质母细胞瘤（GBM）试验中使用外部对照的一个潜在局限性。在本研究中，我们评估了在过去二十年间，在临床试验中接受标准斯图普方案治疗的新诊断胶质母细胞瘤（ndGBM）患者的预后是否发生了变化。在考虑主要预后因素后，过去二十年间的3期GBM试验未观察到时间趋势偏倚的证据。

REF: Sferruzza G, Desingu K, Cubero Cruz A, Finocchiaro G. Assessing time-trend bias in glioblastoma prognosis over two decades of clinical trials. Neuro Oncol. Published online June 28, 2025. doi:10.1093/neuonc/noaf158 PMID: 40580109

CAF-derived LRRC15 orchestrates macrophage polarization and limits PD-1 immunotherapy efficacy in glioblastomaGet accessArrow

癌相关成纤维细胞（CAF）来源的LRRC15调控巨噬细胞极化并限制胶质母细胞瘤中PD - 1免疫治疗的疗效 获取权限 箭头

The effectiveness of PD-1/PD-L1 immune checkpoint blockade therapy in glioblastoma (GBM) is limited due to the tumor immunosuppressive microenvironment (TIME). Therefore, strategies of reprogramming TIME to a proinflammatory state offers a promising therapeutic approach. Our findings suggest that targeting LRRC15 may provide a novel strategy to augment anti-PD-1 therapy and overcome immunotherapy resistance in GBM.

由于肿瘤免疫抑制微环境（TIME）的存在，程序性死亡蛋白 1（PD - 1）/程序性死亡配体 1（PD - L1）免疫检查点阻断疗法在胶质母细胞瘤（GBM）中的疗效有限。因此，将肿瘤免疫抑制微环境重编程为促炎状态的策略提供了一种有前景的治疗方法。我们的研究结果表明，靶向富含亮氨酸重复序列蛋白 15（LRRC15）可能为增强抗 PD - 1 治疗并克服胶质母细胞瘤的免疫治疗耐药性提供一种新策略。

REF: Luo F, Mei Y, Li Y, et al. CAF-derived LRRC15 orchestrates macrophage polarization and limits PD-1 immunotherapy efficacy in glioblastoma. Neuro Oncol. Published online June 26, 2025. doi:10.1093/neuonc/noaf157 PMID: 40569145

Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development

轨迹分析揭示了MYCN驱动的神经母细胞瘤发展过程中的一种未定向神经母细胞状态

Understanding the factors that determine the spontaneous regression of pre-cancerous lesions is critical to advancing cancer prevention. Neuroblastoma, a pediatric cancer, undergoes spontaneous regression more frequently than other types of cancer. Collectively, the identification of this novel neuroblastoma-related cell subtype and its transcriptomic signature not only enhances our understanding of spontaneous regression mechanisms but also holds potential for therapeutic advancements in treating neuroblastomas.

了解决定癌前病变自发消退的因素对于推动癌症预防至关重要。神经母细胞瘤是一种儿童癌症，相较于其他类型的癌症，它更常发生自发消退。总体而言，对这种新型神经母细胞瘤相关细胞亚型及其转录组特征的鉴定，不仅加深了我们对自发消退机制的理解，还为神经母细胞瘤的治疗进展带来了潜在的希望。

REF: Tsubota S, Carter DR, Seneviratne JA, et al. Trajectory analysis reveals an uncommitted neuroblastic state in MYCN-driven neuroblastoma development. Neuro Oncol. Published online June 24, 2025. doi:10.1093/neuonc/noaf129 PMID: 40580553

Plasmablast-like lymphoma cells as a distinct subpopulation confers multidrug resistance in PCNSLGet accessArrow

浆母细胞样淋巴瘤细胞作为一个独特亚群赋予原发性中枢神经系统淋巴瘤多药耐药性 获取权限 箭头

Primary central nervous system lymphoma (PCNSL) is a highly aggressive subtype of non-Hodgkin lymphoma that is confined to the central nervous system. PCNSL is associated with a poor 5-year survival rate of 30-40%, partly due to a high recurrence rate of 60%. A comprehensive understanding of the molecular signatures and mechanisms underlying drug resistance in PCNSL is crucial, as it has significant implications for therapeutic strategies. These findings highlight PBLCs as a distinct subtype of malignant B cells that plays a critical role in the multidrug resistance of PCNSL and reveal the molecular signature of PBLCs that can be targeted for therapy.

原发性中枢神经系统淋巴瘤（PCNSL）是一种高度侵袭性的非霍奇金淋巴瘤亚型，局限于中枢神经系统。PCNSL的5年生存率较低，为30 - 40%，部分原因是复发率高达60%。全面了解PCNSL耐药的分子特征和机制至关重要，因为这对治疗策略具有重要意义。这些发现凸显了浆母细胞样B细胞（PBLCs）是恶性B细胞的一种独特亚型，其在PCNSL的多药耐药中起关键作用，并揭示了可作为治疗靶点的PBLCs分子特征。

REF: Liang F, Zhang X, Ping A, et al. Plasmablast-like lymphoma cells as a distinct subpopulation confers multidrug resistance in PCNSL. Neuro Oncol. Published online June 21, 2025. doi:10.1093/neuonc/noaf154 PMID: 40580931

Glioportal: a comprehensive transcriptomic resource unveiling ligand-mediated mesenchymal transition in glioblastoma

神经胶质瘤门户：一个揭示胶质母细胞瘤中配体介导的间充质转化的综合转录组学资源库

Multi-omics profiling of glioblastoma (GBM) has unravelled two aspects fundamental to its aggressiveness and lethality that is molecular heterogeneity inherent to the tumour and cellular plasticity modulated by microenvironment. Yet, empirical validation to identify causal factors for these complex mechanisms is rather scarce. Here, we report our endeavour in establishing Glioportal, a GBM tumour biobank with derivative preclinical models and molecular information that we leverage for basic and translational research on precision therapies. Glioportal makes a valuable resource for identifying therapeutic vulnerabilities in molecularly stratified GBM. Here, we underscore GBM dependency on myeloid-derived ligands to acquire mesenchymal traits that has clinical implications in therapeutic response and recurrence. Such reliance warrants treatment strategies targeting ligand-receptor pairs to mitigate interactions with tumour ecosystem.

胶质母细胞瘤（GBM）的多组学分析揭示了其侵袭性和致死性的两个基本方面，即肿瘤固有的分子异质性以及由微环境调节的细胞可塑性。然而，用于确定这些复杂机制因果因素的实证验证相当匮乏。在此，我们报告了我们建立“神经胶质瘤库（Glioportal）”的努力，这是一个拥有衍生临床前模型和分子信息的GBM肿瘤生物样本库，我们利用它来开展精准治疗的基础研究和转化研究。神经胶质瘤库是识别分子分层GBM治疗靶点的宝贵资源。在此，我们强调GBM依赖髓系来源的配体来获得间充质特征，这对治疗反应和复发具有临床意义。这种依赖性促使我们制定针对配体 - 受体对的治疗策略，以减少与肿瘤生态系统的相互作用。

REF: Pang QY, Novera W, Koh LWH, et al. Glioportal: a comprehensive transcriptomic resource unveiling ligand-mediated mesenchymal transition in glioblastoma. Neuro Oncol. Published online June 16, 2025. doi:10.1093/neuonc/noaf145 PMID: 40518441

Cranial radiotherapy profoundly affects glia without inducing widespread cellular senescenceGet accessArrow

颅脑放疗会对神经胶质细胞产生深远影响，但不会诱导广泛的细胞衰老 获取权限 箭头（注：“箭头”可能是原文有特定含义的图标等对应表述，需结合原文语境确定更准确译法）

More than 70% of cancer patients who underwent cranial radiotherapy have cognitive problems, suggesting that they might undergo accelerated brain aging due to the cancer treatment. Radiotherapy is known to induce cellular senescence in tumors and in various cell types in vitro. Therefore, we hypothesized that cranial radiotherapy induces cellular senescence in the brain. Overall, cellular senescence in the healthy brain seems a rather uncommon phenomenon and not induced upon cranial radiotherapy, but profound changes in different types of glia were detected upon cranial radiotherapy.

超过70%接受颅脑放疗的癌症患者存在认知问题，这表明他们可能因癌症治疗而出现大脑加速衰老的情况。众所周知，放疗会在体外诱导肿瘤细胞和多种细胞类型发生细胞衰老。因此，我们推测颅脑放疗会诱导大脑发生细胞衰老。总体而言，健康大脑中的细胞衰老似乎是一种相当罕见的现象，且不会因颅脑放疗而诱发，但在进行颅脑放疗后，不同类型的神经胶质细胞会发生显著变化。

REF: Kuil LE, van Scheppingen RH, Leter YM, et al. Cranial radiotherapy profoundly affects glia without inducing widespread cellular senescence. Neuro Oncol. Published online June 16, 2025. doi:10.1093/neuonc/noaf146 PMID: 40518745

Years of life lost due to central nervous system tumor subtypes in the United StatesGet accessArrow

美国因中枢神经系统肿瘤亚型导致的寿命损失年数 获取权限 箭头

Years of Life Lost (YLL) is a disease burden measure quantifying the number of years lost due to premature mortality for a given disease. The present study sought to assess YLL for primary brain and other central nervous system (CNS) tumor histopathologies in the United States. Malignant CNS tumors, glioblastoma in particular, contributed the most to total YLL, whereas pediatric CNS malignancies had the greatest mYLL. Used with other epidemiological data, the authors contend that this quantification may help rationalize allocation of clinical and research resources.

潜在寿命损失年（YLL）是一种疾病负担衡量指标，用于量化因特定疾病导致的过早死亡所损失的年数。本研究旨在评估美国原发性脑及其他中枢神经系统（CNS）肿瘤组织病理学类型的潜在寿命损失年。恶性中枢神经系统肿瘤，尤其是胶质母细胞瘤，对总潜在寿命损失年的贡献最大，而儿童中枢神经系统恶性肿瘤的平均潜在寿命损失年（mYLL）最高。作者认为，将这一量化结果与其他流行病学数据结合使用，可能有助于合理分配临床和研究资源。

REF: Gerstl JVE, Price M, Bernstock JD, et al. Years of life lost due to central nervous system tumor subtypes in the United States. Neuro Oncol. Published online June 15, 2025. doi:10.1093/neuonc/noaf142 PMID: 40517297