Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Center for Neuro-Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Nat Rev Cancer. 2021 Dec;21(12):786-802. doi: 10.1038/s41568-021-00397-3. Epub 2021 Sep 28.
Brain cancers carry bleak prognoses, with therapeutic advances helping only a minority of patients over the past decade. The brain tumour microenvironment (TME) is highly immunosuppressive and differs from that of other malignancies as a result of the glial, neural and immune cell populations that constitute it. Until recently, the study of the brain TME was limited by the lack of methods to de-convolute this complex system at the single-cell level. However, novel technical approaches have begun to reveal the immunosuppressive and tumour-promoting properties of distinct glial and myeloid cell populations in the TME, identifying new therapeutic opportunities. Here, we discuss the immune modulatory functions of microglia, monocyte-derived macrophages and astrocytes in brain metastases and glioma, highlighting their disease-associated heterogeneity and drawing from the insights gained by studying these malignancies and other neurological disorders. Lastly, we consider potential approaches for the therapeutic modulation of the brain TME.
脑癌预后不佳,在过去十年中,治疗进展仅帮助少数患者。脑肿瘤微环境(TME)高度免疫抑制,与其他恶性肿瘤不同,因为它由神经胶质细胞、神经元和免疫细胞组成。直到最近,由于缺乏在单细胞水平上对这个复杂系统进行去卷积的方法,对脑 TME 的研究受到限制。然而,新的技术方法开始揭示 TME 中不同神经胶质细胞和髓样细胞群的免疫抑制和肿瘤促进特性,为新的治疗机会提供了线索。在这里,我们讨论了小胶质细胞、单核细胞衍生的巨噬细胞和星形胶质细胞在脑转移和神经胶质瘤中的免疫调节功能,强调了它们与疾病相关的异质性,并借鉴了研究这些恶性肿瘤和其他神经疾病所获得的见解。最后,我们考虑了治疗性调节脑 TME 的潜在方法。