乳腺癌脑转移（BCBM）是一种致命的疾病，没有有效的治疗方法。先前的研究表明，脑癌和转移瘤密集地浸润着抗炎、促肿瘤的肿瘤相关巨噬细胞，但大脑驻留小胶质细胞的作用仍然存在争议，因为它们很难与其他肿瘤相关巨噬细胞区分开来。利用单细胞 RNA 测序、遗传和人源化小鼠模型，我们专门鉴定了小胶质细胞，并发现它们在 BCBM 中发挥着独特的促炎和肿瘤抑制作用。缺乏小胶质细胞的动物表现出转移增加、存活率降低以及自然杀伤细胞和 T 细胞反应减少，这表明小胶质细胞对于促进抗肿瘤免疫以抑制 BCBM 至关重要。我们发现促炎症反应在人类小胶质细胞中是保守的，并且其反应标志物与 BCBM 患者更好的预后相关。这些发现确立了小胶质细胞在抗肿瘤免疫中的重要作用，并强调它们作为脑转移的潜在免疫治疗靶点。© 2023。作者，获得 Springer Nature Limited 的独家许可。

Breast cancer brain metastasis (BCBM) is a lethal disease with no effective treatments. Prior work has shown that brain cancers and metastases are densely infiltrated with anti-inflammatory, protumourigenic tumour-associated macrophages, but the role of brain-resident microglia remains controversial because they are challenging to discriminate from other tumour-associated macrophages. Using single-cell RNA sequencing, genetic and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumour-suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival and reduced natural killer and T cell responses, showing that microglia are critical to promote anti-tumour immunity to suppress BCBM. We find that the pro-inflammatory response is conserved in human microglia, and markers of their response are associated with better prognosis in patients with BCBM. These findings establish an important role for microglia in anti-tumour immunity and highlight them as a potential immunotherapy target for brain metastasis.© 2023. The Author(s), under exclusive licence to Springer Nature Limited.