脑转移中的免疫景观。
The Immune Landscape in Brain Metastasis.
发表日期:2024 Oct 15
作者:
Luca D Schreurs, Alexander F Vom Stein, Stephanie T Jünger, Marco Timmer, Ka-Won Noh, Reinhard Buettner, Hamid Kashkar, Volker Neuschmelting, Roland Goldbrunner, Phuong-Hien Nguyen
来源:
NEURO-ONCOLOGY
摘要:
尽管经过手术切除、放疗、化疗、靶向治疗和免疫治疗等强化治疗,脑转移患者的预后仍然很差。因此,对于新的治疗选择存在很高的医学需求。采用高通量和空间分辨单细胞分析的最新进展为转移性脑中不同免疫细胞的组成和表型提供了前所未有的见解,揭示了与原发性脑肿瘤或其他转移部位截然不同的独特免疫景观。这篇综述总结了关于脑转移微环境中最重要的免疫细胞的组成和表型的当前证据,以及它们与转移肿瘤细胞和彼此之间的动态相互作用。作为该领域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的表型异质性和功能可塑性,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。我们还回顾了评估针对脑转移的免疫微环境的治疗潜力的临床前和临床试验。鉴于大量证据强调免疫微环境生态位在脑转移发病机制中的重要作用,全面了解该生态位内的关键分子和细胞因素为开发脑转移的新治疗方法和创新组合治疗策略带来了巨大希望。 © 作者 2024。由牛津大学出版社代表神经肿瘤学会出版。
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 tumours or other metastatic sites. This review summarises 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 tumour 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 tumour-associated macrophages, including both resident microglia and monocyte-derived macrophages, as well as the T-cell compartment. We also review pre-clinical 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.© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.