Duke Medical School, Duke University Medical Center, Durham, NC, United States.
Preston Robert Tisch Brain Tumor Center at Duke, Department of Neurosurgery, Duke University Medical Center, Durham, NC, United States.
Adv Drug Deliv Rev. 2022 Jun;185:114311. doi: 10.1016/j.addr.2022.114311. Epub 2022 Apr 27.
Immunotherapies, such as immune checkpoint inhibition (ICI), have had limited success in treating intracranial malignancies. These failures are due partly to the restrictive blood-brain-barrier (BBB), the profound tumor-dependent induction of local and systemic immunosuppression, and immune evasion exhibited by these tumors. Therefore, novel approaches must be explored that aim to overcome these stringent barriers. LITT is an emerging treatment for brain tumors that utilizes thermal ablation to kill tumor cells. LITT provides an additional therapeutic benefit by synergizing with ICI and systemic chemotherapies to strengthen the anti-tumor immune response. This synergistic relationship involves transient disruption of the BBB and local augmentation of immune function, culminating in increased CNS drug penetrance and improved anti-tumor immunity. In this review, we will provide an overview of the challenges facing immunotherapy for brain tumors, and discuss how LITT may synergize with the endogenous anti-tumor response to improve the efficacy of ICI.
免疫疗法,如免疫检查点抑制(ICI),在治疗颅内恶性肿瘤方面的效果有限。这些失败部分归因于血脑屏障(BBB)的限制、局部和全身免疫抑制的深刻肿瘤依赖性诱导,以及这些肿瘤表现出的免疫逃逸。因此,必须探索新的方法,旨在克服这些严格的障碍。LITT 是一种新兴的脑肿瘤治疗方法,利用热消融来杀死肿瘤细胞。LITT 通过与 ICI 和全身化疗协同作用来增强抗肿瘤免疫反应,提供额外的治疗益处。这种协同关系涉及 BBB 的短暂破坏和局部免疫功能的增强,最终导致 CNS 药物渗透性增加和抗肿瘤免疫增强。在这篇综述中,我们将概述脑肿瘤免疫治疗面临的挑战,并讨论 LITT 如何与内源性抗肿瘤反应协同作用,以提高 ICI 的疗效。