Nishioka Kentaro, Kawamura Mariko, Iima Mami, Ueda Daiju, Ito Rintaro, Saida Tsukasa, Kurokawa Ryo, Takumi Koji, Sakata Akihiko, Ide Satoru, Honda Maya, Yanagawa Masahiro, Sugawara Shunsuke, Oda Seitaro, Watabe Tadashi, Sofue Keitaro, Hirata Kenji, Naganawa Shinji
Radiation Oncology Division, Global Center for Biomedical Science and Engineering, Faculty of Medicine, Hokkaido University, Nishi 7, Kita 15, Kita-ku, Sapporo, Hokkaido, 060-8638, Japan.
Department of Radiology, Nagoya University Graduate School of Medicine, Tsurumai-cho 65, Showa-ku, Nagoya, Aichi, 466-8550, Japan.
J Radiat Res. 2025 Jul 22;66(4):343-353. doi: 10.1093/jrr/rraf027.
The brain and spinal cord, which constitute the central nervous system, were historically considered immune-privileged sites, as it was believed they lacked an equivalent to the systemic lymphatic system. However, in 2013, a pathway facilitating the clearance of waste products through the brain parenchyma via the perivascular space was proposed, garnering attention as the 'glymphatic system'. Similar to the systemic lymphatic system, the glymphatic system plays a critical role in immune responses and has been implicated not only in Alzheimer's disease and inflammatory brain disorders but also in conditions such as hydrocephalus and glaucoma, which are associated with cerebrospinal fluid circulation impairments. Recent studies have suggested that dysfunction of the glymphatic system may promote the progression of brain tumors and reduce the efficacy of immune responses and pharmacological therapies targeting tumors. Radiotherapy is a major treatment option for brain tumors; however, while it can enhance immune responses against tumors, it may also suppress these responses at the same time. Additionally, cranial irradiation has been suggested to impair the function of the glymphatic system. This review provides an overview of the structure and functional evaluation methods of the glymphatic system, summarizes the effects of its dysfunction on brain tumor treatment, and explores recent findings on the impact of radiation therapy on glymphatic system functioning. Lastly, it also explores the potential for radiation therapy strategies that account for their effects on the glymphatic system.
大脑和脊髓构成中枢神经系统，在历史上被认为是免疫特权部位，因为人们认为它们缺乏与全身淋巴系统相当的结构。然而，2013年，有人提出了一条通过血管周围间隙促进脑实质清除废物的途径，即“类淋巴系统”，引起了人们的关注。与全身淋巴系统类似，类淋巴系统在免疫反应中起关键作用，不仅与阿尔茨海默病和炎症性脑部疾病有关，还与脑积水和青光眼等与脑脊液循环障碍相关的病症有关。最近的研究表明，类淋巴系统功能障碍可能促进脑肿瘤的进展，并降低针对肿瘤的免疫反应和药物治疗的疗效。放射治疗是脑肿瘤的主要治疗选择；然而，虽然它可以增强针对肿瘤的免疫反应，但同时也可能抑制这些反应。此外，有人认为头部放疗会损害类淋巴系统的功能。本综述概述了类淋巴系统的结构和功能评估方法，总结了其功能障碍对脑肿瘤治疗的影响，并探讨了放疗对类淋巴系统功能影响的最新研究结果。最后，还探讨了考虑到放疗对类淋巴系统影响的放疗策略的潜力。
