Biomedicine & Pharmacotherapy最新文献

英文中文

CD44 receptor-driven graphene oxide based nanocarriers for cancer therapy CD44受体驱动的氧化石墨烯纳米载体用于癌症治疗

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119036

Ludmila Žárská , Michaela Gapčová , Zuzana Chaloupková , Václav Ranc

Interactions between hyaluronic acid (HA) and the CD44 receptor represent a key mechanism in tumor cell recognition and selective drug uptake. In this study, we compare the efficacy of a graphene oxide (GO)-based nanoplatform in two cell lines with markedly different CD44 expression levels. The aim is to investigate how HA functionalization and its concentration influence the biological behavior of these GO nanocarriers designed for targeted delivery of doxorubicin (DOX). The nanoplatform was prepared by sequential PEGylation of nanosized GO, followed by HA conjugation at three concentrations (0.1, 1, and 10 mg/mL) and subsequent DOX loading. Spectroscopic and microscopic analyses confirmed stepwise surface modification, formation of a stable polymer coating, and successful DOX incorporation through π–π stacking and hydrogen bonding. Biological assays demonstrated that HA enhances CD44-mediated internalization and increases anticancer activity in CD44⁺ HT-1080 cells, while the GO@PEG carrier alone showed minimal cytotoxicity, highlighting its good biocompatibility. In contrast, CD44⁻ SKBR3 cells displayed limited uptake and higher viability, consistent with weaker HA–CD44 interactions and lower receptor expression. Confocal microscopy and Raman spectroscopy visualized effective intracellular accumulation and perinuclear localization of the nanocarrier, further confirming selective internalization mechanisms. Overall, the results provide important insight into the role of HA in improving the specificity, cellular uptake, and safety of GO-based nanoplatforms. The study underscores the significance of CD44 receptor levels in determining therapeutic efficiency and supports the development of receptor-targeted, biocompatible nanocarrier systems for precision cancer therapy.

透明质酸（HA）和CD44受体之间的相互作用是肿瘤细胞识别和选择性药物摄取的关键机制。在这项研究中，我们比较了氧化石墨烯（GO）纳米平台在两种CD44表达水平明显不同的细胞系中的效果。目的是研究透明质酸功能化及其浓度如何影响这些氧化石墨烯纳米载体的生物学行为，这些纳米载体设计用于靶向递送阿霉素（DOX）。纳米平台是通过纳米氧化石墨烯的顺序聚乙二醇化制备的，然后在三种浓度（0.1、1和10 mg/mL）下进行HA偶联，然后加载DOX。光谱和微观分析证实了逐步的表面改性，形成了稳定的聚合物涂层，并通过π -π堆叠和氢键成功地将DOX掺入。生物学实验表明，HA增强CD44介导的内化，增加CD44 + HT-1080细胞的抗癌活性，而GO@PEG载体单独表现出最小的细胞毒性，突出了其良好的生物相容性。相反，CD44 - SKBR3细胞表现出有限的摄取和更高的活力，与较弱的HA-CD44相互作用和较低的受体表达一致。共聚焦显微镜和拉曼光谱显示了纳米载体在细胞内的有效积累和核周定位，进一步证实了选择性内化机制。总的来说，这些结果为透明质酸在提高氧化石墨烯纳米平台的特异性、细胞摄取和安全性方面的作用提供了重要的见解。该研究强调了CD44受体水平在决定治疗效率中的重要性，并支持了受体靶向、生物相容性纳米载体系统用于精确癌症治疗的发展。

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引用次数: 0

Retraction notice to “Experimental study of blood pressure and its impact on spontaneous hypertension in rats with Xin Mai Jia” [Biomed. Pharmacother. 112 (2019) 108689] 《心脉佳对大鼠血压及其对自发性高血压影响的实验研究》[生物医学杂志]。药学杂志，112(2019)108689。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.118992

Yun Jing , Jiajing Hu , Jierong Zhao , Jing Yang , Ning Huang , Ping Song , Jian Xu , Mingxiang Zhang , Peng Li , Yaling Yin

引用次数: 0

Corrigendum to “Multimodal immune profiling of peripheral blood to predict the response to intra-articular autologous blood-derived orthobiologic treatment in patients with knee osteoarthritis” [Biomed. Pharmacother. 192 (2025) 118674] “外周血多模态免疫谱预测膝关节骨性关节炎患者对关节内自体血液来源的骨科治疗的反应”的更正[生物医学杂志]。药学。192 (2025)118674]

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2025.118939

Antonio Tonutti , Valentina Granata , Veronica Marrella , Chiara Camisaschi , Simone Puccio , Emanuela Morenghi , Rita Ragusa , Cristiano Sconza , Nicola Rani , Giuseppe Filardo , Berardo Di Matteo , Carlo Selmi , Cristina Sobacchi , Angela Ceribelli

引用次数: 0

Corrigendum to “Oregano polyphenols reduce human insulin amyloid aggregation” Biomed. Pharmacother. 184 (2025) 117904 《牛至多酚减少人类胰岛素淀粉样蛋白聚集》的勘误表。药学。184(2025)117904。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119066

Silvia Bittner Fialová , Miroslav Gančár , Elena Kurin , Svetlana Dokupilová , Zuzana Gažová , Milan Nagy

引用次数: 0

Retraction notice to “Stachydrine promotes angiogenesis by regulating the VEGFR2/MEK/ERK and mitochondrial-mediated apoptosis signaling pathways in human umbilical vein endothelial cells” [Biomed. Pharmacother. 131 (2020) 110724] 关于“水苏碱通过调节人脐静脉内皮细胞VEGFR2/MEK/ERK和线粒体介导的细胞凋亡信号通路促进血管生成”的撤回通知[Biomed]。药理学杂志，131(2020)110724。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119033

Fei Zhou , Fei Liu , Juan Liu , Yu-Lin He , Qin-Mei Zhou , Li Guo , Cheng Peng , Liang Xiong

引用次数: 0

Differential effects of the anti-obesity drug tirzepatide on adipose tissues: Brown fat as a key target 抗肥胖药物替西肽对脂肪组织的差异作用：棕色脂肪为关键靶点。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119057

Alberto Mestres-Arenas , Tania Quesada-López , Albert Blasco-Roset , Marta Giralt , Francesc Villarroya , Anna Planavila , Marion Peyrou

Tirzepatide is an anti-obesity drug based on dual agonism of the incretin receptors GLP-1R and GIPR. Its anti-obesity effect is largely based on its action of reducing food intake. However, there are indications that tirzepatide exerts effects on adipose tissues beyond those resulting from fat loss due to reduced food intake. To investigate this, we treated mice, previously been made obese through high-fat diet, with tirzepatide. We also established an experimental group of mice pair-fed with those treated with tirzepatide, key to distinguish the specific effect of tirzepatide from food intake reduction-mediated effects. Both groups experienced similar reduction in body weight, with a trend toward greater loss in visceral and subcutaneous white fat in mice under tirzepatide treatment. Glucose tolerance improved in tirzepatide-treated obese mice, independently of reduced food intake. Tirzepatide treatment also lowered the inflammatory status of obese mice, which in this case, was attributable to decreased food consumption. Tirzepatide exerted distinct effects on brown adipose tissue relative to white adipose tissues, significantly boosting thermogenic activity and modifying its gene expression pattern, including the upregulation of genes linked to thermogenesis and substrate oxidation. White adipose tissues responded differently, being primarily affected in their lipid metabolism. These effects were specific to tirzepatide treatment and not attributable to reduced food intake. Our results indicate that tirzepatide affects the function and metabolism of adipose tissues and especially induces activation of brown adipose tissue in mice, which may be relevant for future human studies to ascertain the mechanisms of tirzepatide metabolic benefits.

替西肽是一种基于肠促胰岛素受体GLP-1R和GIPR双重激动作用的抗肥胖药物。它的抗肥胖作用主要是基于它减少食物摄入的作用。然而，有迹象表明，替西肽对脂肪组织的影响超出了因减少食物摄入而导致的脂肪减少。为了研究这一点，我们用替西帕肽治疗了先前通过高脂肪饮食导致肥胖的小鼠。我们还建立了一个实验组，与替西肽治疗的小鼠配对喂养，以区分替西肽的特异性作用与食物摄入减少介导的作用。在替西肽治疗下，两组小鼠的体重都有相似的减少，内脏和皮下白色脂肪的减少趋势更大。替西肽治疗的肥胖小鼠的葡萄糖耐量得到改善，与减少食物摄入量无关。替西帕肽治疗还降低了肥胖小鼠的炎症状态，在这种情况下，这是由于减少了食物消耗。相对于白色脂肪组织，替西帕肽对棕色脂肪组织有明显的影响，显著提高了产热活性，并改变了其基因表达模式，包括与产热和底物氧化相关的基因上调。白色脂肪组织的反应不同，主要受到脂质代谢的影响。这些效果是替西肽治疗特有的，与减少食物摄入无关。我们的研究结果表明，替西肽影响小鼠脂肪组织的功能和代谢，特别是诱导棕色脂肪组织的激活，这可能与未来的人体研究有关，以确定替西肽代谢益处的机制。

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引用次数: 0

V-domain immunoglobulin suppressor of T-cell activation regulates CD4+ T cell activation and podocyte function through PI3K/AKT signaling pathway T细胞活化的v域免疫球蛋白抑制因子通过PI3K/AKT信号通路调控CD4+ T细胞活化和足细胞功能

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119038

Zhijie Luo , Qiqi Zhang , Tingting Zhang , Tianyi Yuan , Dingyi Yuan , Xueyan Zhao , Ting Gao , Ruixue Ma , Hai Qian , Xinzhi Wang , Jun Liu

The activation of V-domain immunoglobulin suppressor of T-cell activation (VISTA) has shown its therapeutic potential in murine lupus-like disease through immunoregulation, particularly suppressing CD4⁺ T cell activation. Podocytes are critical for preventing proteinuria in lupus nephritis (LN). However, the mechanisms by which VISTA regulate CD4⁺ T cells and renal podocytes remain unclear. Here, we demonstrated that CD4⁺ T cells from VISTA knockout mice showed upregulated phosphorylation of PI3K/AKT, increased secretion of IFN-γ, IL-17 and CD40L. Soluble VISTA mitigated inflammation and recovered the expression of structural proteins Podocin through inhibition of PI3K/AKT/mTOR signaling pathway and induction of autophagy. Moreover, previously demonstrated VISTA agonist Baloxavir marboxil decreased renal CD4⁺ T cells, restored the expression of Nephrin and Podocin, and promoted autophagy. Our study suggests that VISTA plays an important role in the pathogenesis of LN, which offers novel mechanisms and potential target for its application in LN therapy.

v域免疫球蛋白T细胞活化抑制因子（VISTA）的激活通过免疫调节，特别是抑制CD4+ T细胞活化，在小鼠狼疮样疾病中显示出其治疗潜力。足细胞是预防狼疮肾炎（LN）蛋白尿的关键。然而，VISTA调节CD4+ T细胞和肾足细胞的机制尚不清楚。在这里，我们证明了VISTA敲除小鼠的CD4+ T细胞表现出PI3K/AKT磷酸化上调，IFN-γ、IL-17和CD40L分泌增加。可溶性VISTA通过抑制PI3K/AKT/mTOR信号通路，诱导自噬，减轻炎症，恢复结构蛋白Podocin的表达。此外，先前证实的VISTA激动剂Baloxavir marboxil可降低肾CD4+ T细胞，恢复Nephrin和Podocin的表达，促进自噬。我们的研究表明，VISTA在LN的发病机制中发挥了重要作用，为其在LN治疗中的应用提供了新的机制和潜在的靶点。

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引用次数: 0

Myeloid-specific Exoc5 deficiency develops renal inflammation and hypertension 骨髓特异性Exoc5缺乏可导致肾脏炎症和高血压

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119061

Gwan Beom Lee , Ga-Eun Yoon , Phuong Quynh Luong , Masumi Eto , Joshua H. Lipschutz , Jee In Kim

Migration of macrophages into the kidney is a cause of inflammation and the pathogenesis of hypertension. The exocyst complex drives polarized exocytosis and cell migration, although the roles of the exocyst complex in macrophage infiltration have yet to be fully understood. Here, we determined the pathophysiological role of Exoc5, a major component of the exocyst complex, in the development of hypertension using myeloid-specific Exoc5-deficient (LysM-Exoc5 KO) mice and cells. Selective elimination of Exoc5 expression in bone marrow-derived macrophages (BMDM) of LysM-Exoc5 KO mice elevated blood pressures (BP) compared to WT mice. Simultaneously, elevations in BMDM infiltration and expression of pro-inflammatory markers, such as F4/80, TNF-α, IL-6, and MCP-1, as well as angiotensin II and various sodium transporters, occurred in the kidneys of LysM-Exoc5 KO mice. LysM-Exoc5 KO BMDM demonstrated reduced release of exosomes containing formin1, accumulating formin1 inside the cell, and the enhanced BMDM migration was reversed by an actin disruptor and formin1 inhibitor. On the other hand, levels of Rac1 and GTP-bound Rac1 were unchanged between LysM-Exoc5 KO and WT, nor did the Rac1 inhibitor show any effect on the migration. Silencing the Exoc5 gene in Raw264.7 cells reduced exosome release, leading to the accumulation of formin1 within cells, mimicking the LysM-Exoc5 KO phenotype. Exoc5-downregulated Raw264.7 cells injected into mice migrated into the kidney, inducing inflammation and increasing BP. These findings unravel an Exoc5-mediated selective exocytosis-regulated mechanism of inflammation and hypertension, providing Exoc5 and formin1 as potential therapeutic targets for hypertension.

巨噬细胞迁移到肾脏是引起炎症和高血压的发病机制之一。胞囊复合体驱动极化胞吐和细胞迁移，尽管胞囊复合体在巨噬细胞浸润中的作用尚未完全了解。在这里，我们利用骨髓特异性Exoc5缺陷（LysM-Exoc5 KO）小鼠和细胞，确定了Exoc5（外囊复合物的主要成分）在高血压发展中的病理生理作用。与WT小鼠相比，选择性消除LysM-Exoc5 KO小鼠骨髓源性巨噬细胞（BMDM）中Exoc5表达升高血压（BP）。同时，LysM-Exoc5 KO小鼠肾脏中BMDM浸润和促炎标志物（如F4/80、TNF-α、IL-6和MCP-1）以及血管紧张素II和各种钠转运蛋白的表达升高。LysM-Exoc5 KO BMDM显示含有formin1的外泌体释放减少，在细胞内积累formin1，并且增强的BMDM迁移被肌动蛋白干扰物和formin1抑制剂逆转。另一方面，在LysM-Exoc5 KO和WT之间，Rac1和gtp结合的Rac1的水平没有变化，Rac1抑制剂对迁移也没有任何影响。在Raw264.7细胞中沉默Exoc5基因减少了外泌体的释放，导致形成1在细胞内的积累，模拟了LysM-Exoc5 KO表型。将exoc5下调的Raw264.7细胞注射到小鼠体内，迁移到肾脏，引起炎症并升高血压。这些发现揭示了Exoc5介导的选择性胞吐调节炎症和高血压的机制，提供了Exoc5和formin1作为高血压的潜在治疗靶点。

{"title":"Myeloid-specific Exoc5 deficiency develops renal inflammation and hypertension","authors":"Gwan Beom Lee , Ga-Eun Yoon , Phuong Quynh Luong , Masumi Eto , Joshua H. Lipschutz , Jee In Kim","doi":"10.1016/j.biopha.2026.119061","DOIUrl":"10.1016/j.biopha.2026.119061","url":null,"abstract":"<div><div>Migration of macrophages into the kidney is a cause of inflammation and the pathogenesis of hypertension. The exocyst complex drives polarized exocytosis and cell migration, although the roles of the exocyst complex in macrophage infiltration have yet to be fully understood. Here, we determined the pathophysiological role of Exoc5, a major component of the exocyst complex, in the development of hypertension using myeloid-specific Exoc5-deficient (LysM-Exoc5 KO) mice and cells. Selective elimination of Exoc5 expression in bone marrow-derived macrophages (BMDM) of LysM-Exoc5 KO mice elevated blood pressures (BP) compared to WT mice. Simultaneously, elevations in BMDM infiltration and expression of pro-inflammatory markers, such as F4/80, TNF-α, IL-6, and MCP-1, as well as angiotensin II and various sodium transporters, occurred in the kidneys of LysM-Exoc5 KO mice. LysM-Exoc5 KO BMDM demonstrated reduced release of exosomes containing formin1, accumulating formin1 inside the cell, and the enhanced BMDM migration was reversed by an actin disruptor and formin1 inhibitor. On the other hand, levels of Rac1 and GTP-bound Rac1 were unchanged between LysM-Exoc5 KO and WT, nor did the Rac1 inhibitor show any effect on the migration. Silencing the <em>Exoc5</em> gene in Raw264.7 cells reduced exosome release, leading to the accumulation of formin1 within cells, mimicking the LysM-Exoc5 KO phenotype. Exoc5-downregulated Raw264.7 cells injected into mice migrated into the kidney, inducing inflammation and increasing BP. These findings unravel an Exoc5-mediated selective exocytosis-regulated mechanism of inflammation and hypertension, providing Exoc5 and formin1 as potential therapeutic targets for hypertension.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"195 ","pages":"Article 119061"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074193","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}

引用次数: 0

Cerebral dopamine neurotrophic factor and its functional fragments induce calcium signal through sigma-1 receptor and protect neurons against glutamate-induced excitotoxicity 脑多巴胺神经营养因子及其功能片段通过sigma-1受体诱导钙信号，保护神经元免受谷氨酸诱导的兴奋毒性

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-02-01 DOI: 10.1016/j.biopha.2026.119034

Nafisa Komilova , Noemi Esteras , Alessandra Preziuso , Lauren Millichap , Ausra Domanska , Anastasia Ludwig , Natalia Kulesskaya , Henri J. Huttunen , Kira M. Holmström , Andrey Y. Abramov , Plamena R. Angelova

Cerebral Dopamine Neurotrophic Factor (CDNF) is known to protect neurons in various pathologies. HER-096 is a CDNF-derived brain-penetrating peptidomimetic which also possesses neuroprotective properties. However, the mechanism underlying the cytoprotective effects is not fully understood. Using primary cortical co-culture of neurons and astrocytes we have found that both CDNF and HER-096 can induce intracellular calcium signals predominantly in astrocytes by release of Ca^2 + from endoplasmic reticulum to cytosol. This decrease in the ER Ca²⁺ pool activates store-operated calcium entrance (SOCE). Initial Ca²⁺ signal in these cells could be inhibited by the sigma-1 receptor antagonist BD-1047. CDNF and HER-096 reduced the glutamate-induced delayed Ca²⁺ deregulation and mitochondrial depolarisation which leads to significant protection against glutamate-induced excitotoxicity. Thus, the CDNF and HER-096 sigma-1 receptor mediated Ca²⁺ signal in astrocytes and neurons, from the ER, could modify the effects of high concentrations of glutamate that lead to neuroprotection.

已知脑多巴胺神经营养因子（CDNF）在各种病理中保护神经元。HER-096是一种cdnf衍生的脑穿透类肽，也具有神经保护作用。然而，细胞保护作用的机制尚不完全清楚。通过神经元和星形胶质细胞的原代皮质共培养，我们发现CDNF和HER-096都可以通过从内质网向细胞质溶胶释放Ca2 +来诱导星形胶质细胞内的细胞内钙信号。内质网Ca2+池的减少激活了储运钙入口（SOCE）。这些细胞中的初始Ca2+信号可以被sigma-1受体拮抗剂BD-1047抑制。CDNF和HER-096减少了谷氨酸诱导的延迟Ca2+解除管制和线粒体去极化，这对谷氨酸诱导的兴奋毒性有显著的保护作用。因此，来自内质网的CDNF和HER-096 sigma-1受体介导的星形胶质细胞和神经元中的Ca2+信号可以改变高浓度谷氨酸导致神经保护的作用。

{"title":"Cerebral dopamine neurotrophic factor and its functional fragments induce calcium signal through sigma-1 receptor and protect neurons against glutamate-induced excitotoxicity","authors":"Nafisa Komilova , Noemi Esteras , Alessandra Preziuso , Lauren Millichap , Ausra Domanska , Anastasia Ludwig , Natalia Kulesskaya , Henri J. Huttunen , Kira M. Holmström , Andrey Y. Abramov , Plamena R. Angelova","doi":"10.1016/j.biopha.2026.119034","DOIUrl":"10.1016/j.biopha.2026.119034","url":null,"abstract":"<div><div>Cerebral Dopamine Neurotrophic Factor (CDNF) is known to protect neurons in various pathologies. HER-096 is a CDNF-derived brain-penetrating peptidomimetic which also possesses neuroprotective properties. However, the mechanism underlying the cytoprotective effects is not fully understood. Using primary cortical co-culture of neurons and astrocytes we have found that both CDNF and HER-096 can induce intracellular calcium signals predominantly in astrocytes by release of Ca<sup>2 +</sup> from endoplasmic reticulum to cytosol. This decrease in the ER Ca<sup>2+</sup> pool activates store-operated calcium entrance (SOCE). Initial Ca<sup>2+</sup> signal in these cells could be inhibited by the sigma-1 receptor antagonist BD-1047. CDNF and HER-096 reduced the glutamate-induced delayed Ca<sup>2+</sup> deregulation and mitochondrial depolarisation which leads to significant protection against glutamate-induced excitotoxicity. Thus, the CDNF and HER-096 sigma-1 receptor mediated Ca<sup>2+</sup> signal in astrocytes and neurons, from the ER, could modify the effects of high concentrations of glutamate that lead to neuroprotection.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"195 ","pages":"Article 119034"},"PeriodicalIF":7.5,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146074237","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}

引用次数: 0

Immunotherapeutic advances in pediatric neuroblastoma: Overcoming resistance through biomarker-guided combinations 儿童神经母细胞瘤的免疫治疗进展：通过生物标志物引导组合克服耐药性。

IF 7.5 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Biomedicine & Pharmacotherapy

Pub Date : 2026-01-31 DOI: 10.1016/j.biopha.2026.119020

Mahla Shokouhfar , Ali Darzi , Fatemeh Ameli , Mohammad Taha Nami , Saeed Khavari Khorasani , Pooya Eini , Ahmad Ghorbani Vanan , Nastaran Bahrami

Neuroblastoma is the most common extracranial solid tumor in children. It remains a major therapeutic challenge, particularly in high-risk cases where long-term survival rates remain below 50 % despite intensive multimodal treatment. The immunosuppressive tumor microenvironment (TME), marked by low MHC class I expression and infiltration of regulatory immune cells, has historically limited the efficacy of immune-based therapies. Recent advances in immunotherapy have reshaped the treatment landscape, with anti-GD2 monoclonal antibodies such as dinutuximab and naxitamab demonstrating significant clinical benefit, especially when combined with granulocyte-macrophage colony-stimulating factor (GM-CSF). Beyond antibody-based therapies, new modalities are advancing. CAR T-cell platforms targeting GD2, B7-H3, and L1CAM, along with checkpoint inhibitors, cytokine therapies, cancer vaccines, and oncolytic viruses, are showing early promise. However, resistance mechanisms, such as antigen loss, T-cell exhaustion, and suppressive myeloid populations, continue to hinder durable responses. Biomarkers such as Anaplastic Lymphoma Kinase (ALK) mutation status, immune infiltration profiles, and cytokine signatures are increasingly guiding patient stratification and therapeutic personalization. Combination strategies integrating immunotherapy with chemotherapy, radiotherapy, and targeted agents have demonstrated synergistic potential, and recent clinical trials reflect a shift toward multi-agent regimens. Novel platforms such as armored CARs, bispecific antibodies, and metabolic modulators are expanding the therapeutic horizon. This review synthesizes current evidence on immunotherapeutic strategies in neuroblastoma, highlighting resistance pathways, biomarker-driven approaches, and the evolving clinical trial landscape. Future directions emphasize personalized, biomarker-guided immunotherapy to improve efficacy, reduce toxicity, and establish durable, curative outcomes for children with neuroblastoma.

神经母细胞瘤是儿童最常见的颅外实体瘤。它仍然是一个主要的治疗挑战，特别是在高风险病例中，尽管进行了强化的多模式治疗，但长期生存率仍低于50% %。免疫抑制肿瘤微环境（TME）以低MHC I类表达和调节性免疫细胞浸润为特征，历来限制了免疫治疗的疗效。免疫治疗的最新进展重塑了治疗格局，抗gd2单克隆抗体如迪努妥昔单抗和纳西他单抗显示出显著的临床益处，特别是与粒细胞-巨噬细胞集落刺激因子（GM-CSF）联合使用时。除了基于抗体的治疗之外，新的治疗方式也在不断发展。靶向GD2、B7-H3和L1CAM的CAR - t细胞平台，以及检查点抑制剂、细胞因子疗法、癌症疫苗和溶瘤病毒，正在显示出早期的希望。然而，耐药机制，如抗原丢失、t细胞耗竭和抑制髓细胞群，继续阻碍持久的反应。生物标志物，如间变性淋巴瘤激酶（ALK）突变状态、免疫浸润谱和细胞因子特征，越来越多地指导患者分层和治疗个性化。将免疫治疗与化疗、放疗和靶向药物相结合的联合策略已经显示出协同作用的潜力，最近的临床试验反映了向多药物方案的转变。新的平台，如装甲car、双特异性抗体和代谢调节剂正在扩大治疗的范围。这篇综述综合了神经母细胞瘤免疫治疗策略的现有证据，强调了耐药途径、生物标志物驱动的方法和不断发展的临床试验前景。未来的方向是强调个性化的、生物标志物引导的免疫治疗，以提高儿童神经母细胞瘤的疗效，降低毒性，并建立持久的、治愈的结果。

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