The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5–10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system.

软脑膜是围绕中枢神经系统的充满脑脊液的组织，是各种病症的宿主，包括感染、神经炎症和恶性肿瘤。全身性癌症扩散到这个空间，称为软脑膜转移，发生在 5-10% 的实体瘤患者中，预示着黯淡的临床预后。以前主要是描述性的临床研究几乎没有提供什么见解。最近开发的临床前软脑膜转移模型，以及基因组、转录组和蛋白质组测序工作，为机制理解和确定长期需要的治疗靶点提供了基础。虽然以前被理解为解剖学上孤立的隔室，但软脑膜越来越受到重视，因为它是体循环和中枢神经系统之间交流的主要渠道。尽管软脑膜微环境具有独特的性质，但转移的一般原则是正确的：转移到软脑膜的细胞必须进入新环境，在空间内生存并逃避免疫系统。软脑膜转移的研究有可能揭示新的部位特异性转移原理并阐明软脑膜间隙的生理学。在这篇综述中，我们以生物学为重点，概述了转移细胞如何到达软脑膜，在这种营养稀缺的环境中茁壮成长并逃避无处不在的免疫系统的检测。