Microglia promote anti-tumor immunity and suppress breast cancer brain metastasis

Katrina T Evans, Kerrigan Blake, Aaron Longworth, Morgan A Coburn , Jacob Insua-Rodriguez, Timothy P McMullen, Clare Pridans

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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, protumorigenic tumor associated macrophages (TAMs), but the role of brain resident microglia remains controversial because they are challenging to discriminate from other TAMs. Using single-cell RNA-sequencing (scRNA-seq), genetic, and humanized mouse models, we specifically identify microglia and find that they play a distinct pro-inflammatory and tumor suppressive role in BCBM. Animals lacking microglia show increased metastasis, decreased survival, and reduced NK and T cell responses, showing that microglia are critical to promote antitumor 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 BCBM patients. These findings establish an important role for microglia in anti-tumor immunity and highlight them as a potential immunotherapy target for brain metastasis.
Original languageEnglish
Pages (from-to)1848–1859
JournalNature Cell Biology
Volume25
DOIs
Publication statusPublished - 13 Nov 2023

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