Immunotherapy has enabled remarkable therapeutic responses across cancers of various lineages, albeit with some notable exceptions such as glioblastoma. Several previous misconceptions, which have impaired progress in the past, including the presence and role of the blood–brain barrier and a lack of lymphatic drainage, have been refuted. Nonetheless, a subset of patients with brain metastases but, paradoxically, not the vast majority of those with gliomas are able to respond to immune-checkpoint inhibitors. Immune profiling of samples obtained from patients with central nervous system malignancies using techniques such as mass cytometry and single-cell sequencing along with experimental data from genetically engineered mouse models have revealed fundamental differences in immune composition and immunobiology that not only explain the differences in responsiveness to these agents but also lay the foundations for immunotherapeutic strategies that are applicable to gliomas. Herein, we review the emerging data on the differences in immune cell composition, function and interactions within central nervous system tumours and provide guidance on the development of novel immunotherapies for these historically difficult-to-treat cancers.

免疫疗法对各种谱系的癌症产生了显着的治疗反应，尽管有一些值得注意的例外，例如胶质母细胞瘤。先前的一些误解，包括血脑屏障的存在和作用以及缺乏淋巴引流，这些误解在过去阻碍了进展。尽管如此，一小部分脑转移患者（但矛盾的是，并非绝大多数神经胶质瘤患者）能够对免疫检查点抑制剂产生反应。使用质谱流式细胞仪和单细胞测序等技术对中枢神经系统恶性肿瘤患者的样本进行免疫分析，并结合基因工程小鼠模型的实验数据，揭示了免疫组成和免疫生物学的根本差异，这不仅解释了对免疫反应的差异。这些药物还为适用于神经胶质瘤的免疫治疗策略奠定了基础。在此，我们回顾了有关中枢神经系统肿瘤内免疫细胞组成、功能和相互作用差异的新数据，并为这些历来难以治疗的癌症开发新型免疫疗法提供指导。