Salting the Soil: Targeting the Microenvironment of Brain Metastases.
Salting the Soil: Targeting the Microenvironment of Brain Metastases.
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盐析土壤：针对脑转移的微环境
DOI：
10.1158/1535-7163.mct-20-0579
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发表时间：
2021-03
影响因子：
5.7
通讯作者：
Khasraw M
中科院分区：
文献类型：
--
作者：
Srinivasan ES;Tan AC;Anders CK;Pendergast AM;Sipkins DA;Ashley DM;Fecci PE;Khasraw M
一个多世纪以来，Paget关于转移性传播的“种子和土壤”假说一直是该领域的基础，随着这一过程的机制被阐明，它还在不断进化。通过这个镜头，中枢神经系统呈现出一种独特的土壤，与外周循环和免疫监视相对隔离，具有独特的细胞和结构组成。原发性和转移性脑肿瘤的研究表明，这种肿瘤微环境（tumor microenvironment， TME）在中枢神经系统肿瘤的生长中起着至关重要的作用。在每种情况下，癌细胞都发展出复杂的双向关系，重组局部TME并重新编程中枢神经系统细胞，包括内皮细胞、周细胞、星形胶质细胞、小胶质细胞、浸润性单核细胞和淋巴细胞。这些相互作用产生了结构和免疫上允许的TME，恶性过程促进了正反馈循环和系统性后果。中断与原生中枢神经系统成分的相互作用的策略，在“盐化土壤”上，创造一个不适宜生存的环境，在临床前环境中是有希望的。本综述旨在研究迄今为止在脑胶质瘤中研究的一般和特定途径以及胶质瘤的相关工作，以确定可能在颅内肿瘤谱中具有普遍应用的靶向机制。
Paget’s ‘seed and soil’ hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The CNS presents a unique soil through this lens, relatively isolated from peripheral circulation and immune surveillance with distinct cellular and structural composition. Research in primary and metastatic brain tumors has demonstrated that this tumor microenvironment (TME) plays an essential role in the growth of CNS tumors. In each case, the cancerous cells develop complex and bi-directional relationships that reorganize the local TME and reprogram the CNS cells, including endothelial cells, pericytes, astrocytes, microglia, infiltrating monocytes, and lymphocytes. These interactions create a structurally and immunologically permissive TME with malignant processes promoting positive feedback loops and systemic consequences. Strategies to interrupt interactions with the native CNS components, on 'salting the soil,' to create an inhospitable environment are promising in the preclinical setting. This review aims to examine the general and specific pathways thus far investigated in BrM and related work in glioma to identify targetable mechanisms that may have general application across the spectrum of intracranial tumors.