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高级别胶质瘤的免疫治疗:临床进展及神经外科医生的实践考量

Immunotherapy for High-Grade Gliomas: A Clinical Update and Practical Considerations for Neurosurgeons.

作者信息

Young Jacob S, Dayani Fara, Morshed Ramin A, Okada Hideho, Aghi Manish K

机构信息

Department of Neurological Surgery, University of California, San Francisco, California, USA.

School of Medicine, University of California, San Francisco, California, USA.

出版信息

World Neurosurg. 2019 Apr;124:397-409. doi: 10.1016/j.wneu.2018.12.222. Epub 2019 Jan 22.

Abstract

BACKGROUND

The current standard of care for patients with high-grade gliomas includes surgical resection, chemotherapy, and radiation; but even still most patients experience disease progression and succumb to their illness within a few years of diagnosis. Immunotherapy, which stimulates an anti-tumor immune response, has been revolutionary in the treatment of some hematologic and solid malignancies, generating substantial excitement for its potential for patients with glioblastoma. However, to date, the preclinical success of these approaches against high-grade glioma models has not been replicated in human clinical trials. Moreover, the complex response to these biologically active treatments can complicate management decisions, and the neurosurgical oncology community needs to be actively involved in and up to date on the use of these agents in patients with high-grade glioma. In this review, we discuss the challenges immunotherapy faces for high-grade gliomas, the completed and ongoing clinical trials for the major immunotherapies, and the nuances in management for patients being actively treated with one of these agents.

METHODS

We reviewed the literature to summarize the current immunotherapy strategies for high-grade gliomas.

RESULTS

Preclinical and clinical trials investigating dendritic cell and peptide vaccines, checkpoint inhibitors, and adoptive T cell therapy are highlighted in this review.

CONCLUSIONS

Although immunotherapy has yet to fully fulfill its promise for patients with glioblastoma and improve patient outcomes, there is still excitement that these approaches will eventually lead to durable anti-tumor responses. As neurosurgeons, an understanding of the complex interactions between the standard of care therapies and the other medications used in the treatment arsenal for patients with high-grade brain tumors is crucial to the management of these patients.

摘要

背景

目前,高级别胶质瘤患者的标准治疗方案包括手术切除、化疗和放疗;但即便如此,大多数患者仍会出现疾病进展,并在确诊后的几年内病逝。免疫疗法可激发抗肿瘤免疫反应,在一些血液系统恶性肿瘤和实体瘤的治疗中引发了变革,人们对其治疗胶质母细胞瘤的潜力满怀期待。然而,迄今为止,这些针对高级别胶质瘤模型的临床前研究成果尚未在人类临床试验中得到重现。此外,这些生物活性治疗引发的复杂反应会使治疗决策变得复杂,神经外科肿瘤学界需要积极参与并及时了解这些药物在高级别胶质瘤患者中的应用情况。在本综述中,我们讨论了免疫疗法在治疗高级别胶质瘤时面临的挑战、主要免疫疗法已完成和正在进行的临床试验,以及正在接受其中一种药物积极治疗的患者在管理方面的细微差别。

方法

我们查阅了文献,以总结目前针对高级别胶质瘤的免疫治疗策略。

结果

本综述重点介绍了研究树突状细胞和肽疫苗、检查点抑制剂及过继性T细胞疗法的临床前和临床试验。

结论

尽管免疫疗法尚未完全兑现其对胶质母细胞瘤患者的承诺,也未改善患者的预后,但人们依然期待这些方法最终能带来持久的抗肿瘤反应。作为神经外科医生,了解标准治疗方案与用于治疗高级别脑肿瘤患者的其他药物之间的复杂相互作用,对管理这些患者至关重要。

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