Glial and myeloid heterogeneity in the brain tumour microenvironment

被引:143
作者
Andersen, Brian M. [1 ,2 ]
Akl, Camilo Faust [1 ]
Wheeler, Michael A. [1 ,4 ]
Chiocca, E. Antonio [3 ]
Reardon, David A. [2 ]
Quintana, Francisco J. [1 ,4 ]
机构
[1] Harvard Med Sch, Ann Romney Ctr Neurol Dis, Brigham & Womens Hosp, Boston, MA 02115 USA
[2] Harvard Med Sch, Ctr Neuro Oncol, Dana Farber Canc Inst, Boston, MA 02115 USA
[3] Brigham & Womens Hosp, Dept Neurosurg, 75 Francis St, Boston, MA 02115 USA
[4] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA
关键词
REGULATORY T-CELLS; ENDOTHELIAL GROWTH-FACTOR; ASTROCYTE ACTIVATION; PD-L1; EXPRESSION; DENDRITIC CELLS; RNA-SEQ; INTRATUMORAL HETEROGENEITY; THERAPEUTIC RESISTANCE; REACTIVE ASTROCYTES; GLIOBLASTOMA CELLS;
D O I
10.1038/s41568-021-00397-3
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
This review discusses the immunosuppressive and tumour-promoting properties of microglia, monocyte-derived macrophage and astrocyte subsets in the brain tumour microenvironment, identifying new therapeutic opportunities for primary brain tumours and brain metastases. 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.
引用
收藏
页码:786 / 802
页数:17
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