Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Nat Rev Clin Oncol. 2018 Jul;15(7):422-442. doi: 10.1038/s41571-018-0003-5.
Glioma is the most common primary cancer of the central nervous system, and around 50% of patients present with the most aggressive form of the disease, glioblastoma. Conventional therapies, including surgery, radiotherapy, and pharmacotherapy (typically chemotherapy with temozolomide), have not resulted in major improvements in the survival outcomes of patients with glioblastoma. Reasons for this lack of progress include invasive tumour growth in an essential organ, which limits the utility of local therapy, as well as the protection of tumour cells by the blood-brain barrier, their intrinsic resistance to the induction of cell death, and lack of dependence on single, targetable oncogenic pathways, all of which impose challenges for systemic therapy. Furthermore, the unique immune environment of the central nervous system needs to be considered when pursuing immune-based therapeutic approaches for glioblastoma. Nevertheless, a range of different immunotherapies are currently being actively investigated in patients with this disease, spurred on by advances in immuno-oncology for other tumour types. Herein, we examine the current state of immunotherapy for gliomas, notably glioblastoma, the implications for combining the current standard-of-care treatment modalities with immunotherapies, potential biomarkers of response, and future directions for glioblastoma immuno-oncology.
脑胶质瘤是中枢神经系统最常见的原发性癌症，约 50%的患者患有最具侵袭性的疾病，即胶质母细胞瘤。包括手术、放疗和药物治疗（通常是替莫唑胺化疗）在内的常规疗法并未显著改善胶质母细胞瘤患者的生存结局。造成这种进展缺乏的原因包括肿瘤在重要器官中的侵袭性生长，这限制了局部治疗的效果，以及血脑屏障对肿瘤细胞的保护、肿瘤细胞对细胞死亡诱导的固有抵抗，以及缺乏对单一、可靶向致癌途径的依赖，所有这些都给系统治疗带来了挑战。此外，在为胶质母细胞瘤寻求基于免疫的治疗方法时，需要考虑中枢神经系统的独特免疫环境。尽管如此，由于其他肿瘤类型的免疫肿瘤学的进步，目前正在对多种不同的免疫疗法进行积极研究，以应用于该疾病患者。本文中，我们探讨了当前针对脑胶质瘤，特别是胶质母细胞瘤的免疫疗法的现状，包括将当前的标准治疗模式与免疫疗法相结合的意义、潜在的反应生物标志物，以及胶质母细胞瘤免疫肿瘤学的未来方向。
