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治疗引起的连锁反应:一项探索多形性胶质母细胞瘤远隔效应的系统综述。

Treatment-induced ripple effect: a systematic review exploring the abscopal phenomenon in Glioblastoma multiforme.

作者信息

Bangash Ali Haider, Poudel Prabhat, Alshuqayfi Khalid M, Ahmed Mudassir, Akinduro Oluwaseun O, Essayed Walid Ibn, Salehi Afshin, De la Garza Ramos Rafael, Yassari Reza, Singh Harminder, Sheehan Jason P, Esquenazi Yoshua

机构信息

Hhaider5 Research Group, Rawalpindi, Pakistan.

Spine Research Group, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA.

出版信息

J Neurooncol. 2025 Mar;172(1):77-87. doi: 10.1007/s11060-024-04912-y. Epub 2024 Dec 19.

Abstract

PURPOSE

This systematic review aimed to collate and synthesize the available literature on the abscopal effect in Glioblastoma multiforme (GBM) neoplasms, focusing on the reported biochemical mechanisms driving the abscopal effect.

METHODS

A systematic search was conducted in PubMed, Cochrane Database of Systematic Reviews, and Epistemonikos from inception to May 1, 2023. Studies exploring the abscopal effect in GBM were included. The Clinical Relevance Assessment of Animal Preclinical research (RAA) tool was used to assess methodological quality of preclinical studies. Data on preclinical models, biochemical mechanisms, and outcomes were extracted and synthesized systrmatically.

RESULTS

Out of a total of 7 studies, five preclinical studies met the inclusion criteria. The studies utilized various in vivo mouse models, including bilateral tumor models and immunohumanized mice. Key biochemical mechanisms identified included immunogenic cell death, danger-associated molecular pattern release, macrophage activation, and enhanced T cell responses. Combinatorial approaches involving oncolytic virotherapy, nanoparticle-based treatments, radiation therapy, and immune checkpoint inhibitors showed promise in inducing abscopal effects. Significant tumor growth inhibition and improved survival were reported in treated animals. However, the RAA analysis highlighted concerns regarding research transparency and internal validity across studies.

CONCLUSIONS

This systematic review highlighted the potential of the abscopal effect in GBM, demonstrating its ability to enhance anti-tumor immune responses both locally and systemically. The synergistic effects of combinatorial approaches showed promise for improving outcomes. However, the low methodological quality of existing studies underscored the need for more rigorous preclinical research. Future studies should focus on improving research transparency, exploring the abscopal effect in other primary CNS neoplasms, and translating these findings into clinical trials to assess safety and efficacy in humans.

摘要

目的

本系统评价旨在整理和综合多形性胶质母细胞瘤(GBM)肿瘤中远隔效应的现有文献,重点关注报道的驱动远隔效应的生化机制。

方法

从创刊至2023年5月1日,在PubMed、Cochrane系统评价数据库和Epistemonikos中进行了系统检索。纳入探索GBM中远隔效应的研究。使用动物临床前研究的临床相关性评估(RAA)工具评估临床前研究的方法学质量。系统地提取和综合了关于临床前模型、生化机制和结果的数据。

结果

在总共7项研究中,5项临床前研究符合纳入标准。这些研究使用了各种体内小鼠模型,包括双侧肿瘤模型和免疫人源化小鼠。确定的关键生化机制包括免疫原性细胞死亡、危险相关分子模式释放、巨噬细胞活化和增强的T细胞反应。涉及溶瘤病毒疗法、基于纳米颗粒的治疗、放射疗法和免疫检查点抑制剂的联合方法在诱导远隔效应方面显示出前景。在接受治疗的动物中报告了显著的肿瘤生长抑制和生存期改善。然而,RAA分析突出了对研究透明度和各研究内部有效性的担忧。

结论

本系统评价强调了GBM中远隔效应的潜力,证明了其在局部和全身增强抗肿瘤免疫反应的能力。联合方法的协同效应显示出改善结局的前景。然而,现有研究的方法学质量较低,强调需要更严格的临床前研究。未来的研究应侧重于提高研究透明度,探索其他原发性中枢神经系统肿瘤中的远隔效应,并将这些发现转化为临床试验以评估对人类的安全性和有效性。

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