Department of Neurosurgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Nat Immunol. 2019 Sep;20(9):1100-1109. doi: 10.1038/s41590-019-0433-y. Epub 2019 Jul 29.
Glioblastoma (GBM) is the deadliest form of brain cancer, with a median survival of less than 2 years despite surgical resection, radiation, and chemotherapy. GBM's rapid progression, resistance to therapy, and inexorable recurrence have been attributed to several factors, including its rapid growth rate, its molecular heterogeneity, its propensity to infiltrate vital brain structures, the regenerative capacity of treatment-resistant cancer stem cells, and challenges in achieving high concentrations of chemotherapeutic agents in the central nervous system. Escape from immunosurveillance is increasingly recognized as a landmark event in cancer biology. Translation of this framework to clinical oncology has positioned immunotherapy as a pillar of cancer treatment. Amid the bourgeoning successes of cancer immunotherapy, GBM has emerged as a model of resistance to immunotherapy. Here we review the mechanisms of immunotherapy resistance in GBM and discuss how insights into GBM-immune system interactions might inform the next generation of immunotherapeutics for GBM and other resistant pathologies.
胶质母细胞瘤（GBM）是最致命的脑癌形式，尽管进行了手术切除、放疗和化疗，中位生存期仍不到 2 年。GBM 的快速进展、对治疗的耐药性和不可避免的复发归因于多种因素，包括其快速生长速度、分子异质性、侵袭重要脑结构的倾向、治疗耐药性癌症干细胞的再生能力以及在中枢神经系统中实现化疗药物高浓度的挑战。逃避免疫监视越来越被认为是癌症生物学中的一个标志性事件。这一框架在临床肿瘤学中的转化将免疫疗法定位为癌症治疗的一个支柱。在癌症免疫疗法的蓬勃成功中，GBM 已成为对免疫疗法耐药性的模型。在这里，我们回顾了 GBM 中免疫疗法耐药的机制，并讨论了对 GBM-免疫系统相互作用的深入了解如何为 GBM 和其他耐药性病变的下一代免疫疗法提供信息。
