Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment opti...Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.展开更多
基金Acknowledgments We thank Dr Lena Claesson-Welsh (Uppsala University), and PIs of Model Animal Research Center (MARC, Nanjing University) for the helpful discussion about the work, and Yanlan Cao, Wenting Shi and all the staff in the MARC Animal facility of Nanjing University for excellent technical assistance. This work wasfinancially supported by grants from the National Natural Science Foundation of China (30771069, 30671038, and 30930028), the Ministry of Science and Technology of China (2006CB943500), and the Ministry of Education of China (NCET: Program for New Century Excellent Talents in University).
基金supported by research grants from the National Natural Science Foundation of China(81930011,91739304,and 31821091)the National Key R&D Program of China(2019YFA0801603)+1 种基金supported by a Postdoctoral Fellowship of the Peking-Tsinghua Center for Life Sciencesthe China Postdoctoral Science Foundation(2022T150012).
文摘Glioblastoma(GBM)causes nearly universal mortality as a result of the failure of conventional therapies including surgical resection,targeted radiation therapy,and chemotherapy.An increasingly important treatment option is combining immunotherapy with other therapies in both preclinical and clinical studies.The central nervous system(CNS)has been historically considered an immune privileged area,but increasing evidence,including the recent rediscovery of meningeal lymphatic vessels(MLVs),has overturned this notion.MLVs are populated by multiple immune cells and connect the CNS to the periphery by draining cerebrospinal fluid with soluble CNS antigens and immune cells into cervical lymph nodes.In the past few years,more and more studies have indicated that MLVs are involved in the regulation of inflammation and the immune response in the pathogenesis of various CNS diseases including GBM.Here,we explore the critical interlinkages between MLVs and GBM therapies including chemotherapy,radiotherapy and immunotherapy,and propose the meningeal lymphatic vasculature as a general target for GBM therapy.