biostudies-literatureEvans KTFeodor-Lynen fellowship from the Alexander-von-Humboldt StiftungCanadian Institutes of Health Research Postdoctoral FellowshipNIBIB NIH HHSU.S. Department of Health & Human Services | NIH | National Institute of Neurological Disorders and StrokeU.S. Department of Health & Human Services | NIH | National Cancer InstituteNINDS NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of HealthDivision of Intramural Research, National Institute of Allergy and Infectious DiseasesNIGMS NIH HHS1848-1859https://www.ebi.ac.uk/biostudies/studies/S-EPMC11414741biostudies-literatureUnknown25(12)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 thaNature cell biologyMicroglia promote anti-tumour immunity and suppress breast cancer brain metastasis.PMC11414741U54-CA-217378T32NS121727-01F31 CA281331NIHT32EB009418T32 NS082174K99 CA267160T32NS082174R01 CA237376R01NS1200601K99CA267160-01T32 NS121727T32AI 0602573F31CA281331R01CA237376-01A1T32 GM136624T32 GM008620U54 CA217378R01 NS120060P30 CA062203T32 EB009418T32GM136624Orujyan DMcMullen TPBlurton-Jones MPridans CVillalta SAEvans KTInsua-Rodriguez JLev TBlake KGreen KNCoburn MALongworth ANguyen QHLawson DAEdwards RAMa DOganyan AKHernandez GAfalseMicroglia promote anti-tumour immunity and suppress breast cancer brain metastasis.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 tha2023-01-01T00:00:00Z2023 Dec2026-06-01T10:05:23.356Z2025-04-04T08:22:18.623ZS-EPMC114147413795732410.1038/s41556-023-01273-y