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脑转移瘤的免疫治疗:打破“定论”。

Immunotherapy of brain metastases: breaking a "dogma".

机构信息

Department of Oncology, Center for Immuno-Oncology, Medical Oncology and Immunotherapy, University Hospital of Siena, Viale Bracci, 14, 53100, Siena, Italy.

Unit of Neuroradiology, University Hospital, Siena, Italy.

出版信息

J Exp Clin Cancer Res. 2019 Oct 17;38(1):419. doi: 10.1186/s13046-019-1426-2.

Abstract

Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoclonal antibodies to immune check-point(s) across a wide range of tumor types, patients with brain disease were invariably excluded from clinical trials with these agents. Recent insights on the immune landscape of the central nervous system, as well as of the brain tumor microenvironment, are shedding light on the immune-biology of brain metastases.Interestingly, retrospective analyses, case series, and initial prospective clinical trials have recently investigated the role of different immune check-point inhibitors in brain metastases, reporting a significant clinical activity also in this subset of patients. These findings, and their swift translation in the daily practice, are driving fundamental changes in the clinical management of patients with brain metastases, and raise important neuroradiologic challenges. Along this line, neuro-oncology undoubtedly represents an additional area of active investigation and of growing interest to support medical oncologists in the evaluation of clinical responses of brain metastases to ICI treatment, and in the management of neurologic immune-related adverse events.Aim of this review is to summarize the most recent findings on brain metastases immunobiology, on the evolving scenario of clinical efficacy of ICI therapy in patients with brain metastases, as well as on the increasing relevance of neuroradiology in this therapeutic setting.

摘要

直到几年前,肿瘤学界还顽固地排除了免疫疗法在控制脑转移方面的任何临床潜力。因此,尽管针对多种肿瘤类型的免疫检查点单克隆抗体具有显著的治疗效果,但患有脑部疾病的患者始终被排除在这些药物的临床试验之外。最近对中枢神经系统以及脑肿瘤微环境的免疫景观的深入了解,揭示了脑转移的免疫生物学。有趣的是,最近的回顾性分析、病例系列和初步前瞻性临床试验研究了不同免疫检查点抑制剂在脑转移中的作用,报告了这些患者亚组中也具有显著的临床活性。这些发现及其在日常实践中的迅速转化,正在推动脑转移患者临床管理的根本性变化,并带来重要的神经影像学挑战。在此背景下,神经肿瘤学无疑是一个积极的研究领域,也是一个日益受到关注的领域,旨在支持肿瘤内科医生评估脑转移对 ICI 治疗的临床反应,并管理神经免疫相关不良事件。本综述的目的是总结脑转移免疫生物学的最新发现,以及脑转移患者接受 ICI 治疗的临床疗效不断变化的情况,以及神经影像学在这一治疗环境中的相关性日益增加。

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