University Cancer and Diagnostic Centers, Houston, TX.
Am J Clin Oncol. 2020 Dec 1;43(12):836-845. doi: 10.1097/COC.0000000000000760.
Historically, the brain has been viewed as a specialized neurovascular inert organ with a distinctive immune privilege. Therefore, radiation-induced extracranial abscopal effects would be considered an unusual phenomenon due to the difficulty of the immunogenic signaling molecules to travel across the blood-brain barrier (BBB). However, it is now possible that localized central nervous system radiation has the ability to disrupt the structural integrity of the BBB and increase its endothelial permeability allowing the free passage of immunogenic responses between the intracranial and extracranial compartments. Thus, the nascent tumor-associated antigens produced by localized brain radiation can travel across the BBB into the rest of the body to modulate the immune system and induce extracranial abscopal effects. In clinical practice, localized brain radiation therapy-induced extracranial abscopal effects are a rarely seen phenomenon in metastatic melanoma and other advanced cancers. In this article, we provide a detailed overview of the current state of knowledge and clinical experience of central nervous system radiation-induced extracranial abscopal effects in patients with malignant melanoma. Emerging data from a small number of case reports and cohort studies of various malignancies has significantly altered our earlier understanding of this process by revealing that the brain is neither isolated nor passive in its interactions with the body's immune system. In addition, these studies provide clinical evidence that the brain is capable of interacting actively with the extracranial peripheral immune system. Thus, localized radiation treatment to 1 or more locations of brain metastases can induce extracranial abscopal responses. Collectively, these findings clearly demonstrate that localized brain radiation therapy-induced abscopal effects traverses the BBB and trigger tumor regression in the nonirradiated extracranial locations.
从历史上看，大脑被视为具有独特免疫特权的专门神经血管惰性器官。因此，由于免疫原性信号分子难以穿过血脑屏障 (BBB)，辐射诱导的颅外远隔效应将被认为是一种不寻常的现象。然而，现在可能局部中枢神经系统辐射有能力破坏 BBB 的结构完整性并增加其内皮通透性，允许免疫原性反应在颅内和颅外隔室之间自由通过。因此，局部脑辐射产生的新生肿瘤相关抗原可以穿过 BBB 进入身体的其他部位，调节免疫系统并诱导颅外远隔效应。在临床实践中，局部脑放射治疗诱导的颅外远隔效应在转移性黑色素瘤和其他晚期癌症中是一种罕见现象。在本文中，我们提供了中枢神经系统辐射诱导的恶性黑色素瘤患者颅外远隔效应的当前知识状态和临床经验的详细概述。来自少数病例报告和各种恶性肿瘤队列研究的新兴数据通过揭示大脑在与身体免疫系统的相互作用中既不是孤立的也不是被动的，极大地改变了我们对这一过程的早期理解。此外，这些研究提供了临床证据表明大脑能够与颅外周围免疫系统积极相互作用。因此，对 1 个或多个脑转移部位进行局部放射治疗可以诱导颅外远隔反应。总之，这些发现清楚地表明，局部脑放射治疗诱导的远隔效应穿过 BBB 并触发非照射颅外部位的肿瘤消退。
