Schreurs Luca D, Vom Stein Alexander F, Jünger Stephanie T, Timmer Marco, Noh Ka-Won, Buettner Reinhard, Kashkar Hamid, Neuschmelting Volker, Goldbrunner Roland, Nguyen Phuong-Hien
University of Cologne, Faculty of Medicine and University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf, Cologne, Germany.
University of Cologne, Center for Molecular Medicine Cologne, Cologne, Germany.
Neuro Oncol. 2025 Jan 12;27(1):50-62. doi: 10.1093/neuonc/noae219.
The prognosis for patients with brain metastasis remains dismal despite intensive therapy including surgical resection, radiotherapy, chemo-, targeted, and immunotherapy. Thus, there is a high medical need for new therapeutic options. Recent advances employing high-throughput and spatially resolved single-cell analyses have provided unprecedented insights into the composition and phenotypes of the diverse immune cells in the metastatic brain, revealing a unique immune landscape starkly different from that of primary brain tumors or other metastatic sites. This review summarizes the current evidence on the composition and phenotypes of the most prominent immune cells in the brain metastatic niche, along with their dynamic interactions with metastatic tumor cells and each other. As the most abundant immune cell types in this niche, we explore in detail the phenotypic heterogeneity and functional plasticity of tumor-associated macrophages, including both resident microglia and monocyte-derived macrophages, as well as the T-cell compartment. We also review preclinical and clinical trials evaluating the therapeutic potential of targeting the immune microenvironment in brain metastasis. Given the substantial evidence highlighting a significant role of the immune microenvironmental niche in brain metastasis pathogenesis, a comprehensive understanding of the key molecular and cellular factors within this niche holds great promise for developing novel therapeutic approaches as well as innovative combinatory treatment strategies for brain metastasis.
尽管包括手术切除、放疗、化疗、靶向治疗和免疫治疗在内的强化治疗，脑转移患者的预后仍然很差。因此，对新的治疗选择有很高的医学需求。最近在高通量和空间分辨单细胞分析方面的进展，为转移性脑内多种免疫细胞的组成和表型提供了前所未有的见解，揭示了一种与原发性脑肿瘤或其他转移部位截然不同的独特免疫格局。本综述总结了目前关于脑转移微环境中最突出免疫细胞的组成和表型的证据，以及它们与转移性肿瘤细胞之间及其相互之间的动态相互作用。作为该微环境中最丰富的免疫细胞类型，我们详细探讨了肿瘤相关巨噬细胞（包括常驻小胶质细胞和单核细胞衍生的巨噬细胞）以及T细胞区室的表型异质性和功能可塑性。我们还回顾了评估靶向脑转移免疫微环境治疗潜力的临床前和临床试验。鉴于大量证据突出了免疫微环境在脑转移发病机制中的重要作用，全面了解该微环境中的关键分子和细胞因素，对于开发新的治疗方法以及脑转移的创新联合治疗策略具有很大的前景。
