摘要：SummaryBrain-resident microglia and bone marrow-derived macrophages represent the most abundant non-cancerous cells in the brain tumor microenvironment with critical functions in disease progression and therapeutic response. To date little is known about genetic programs that drive disease-associated phenotypes of microglia and macrophages in brain metastases. Here we used cytometric and transcriptomic analyses to define cellular and molecular changes of the myeloid compartment at distinct stages of brain metastasis and in response to radiotherapy. We demonstrate that genetic programming of tumor education in myeloid cells occurs early during metastatic onset and remains stable throughout tumor progression. Bulk and single cell RNA sequencing revealed distinct gene signatures in brain-resident microglia and blood-borne monocytes/macrophages during brain metastasis and in response to therapeutic intervention. Our data provide a framework for understanding the functional heterogeneity of brain metastasis-associated myeloid cells based on their origin.Graphical AbstractDisplay OmittedHighlights•Tumor education gene signatures arise early during tumor onset and remain stable•TAM-MG and TAM-MDM induce distinct genetic programs in response to tumor education•Radiotherapy enhances the influx of blood-borne myeloid cells•Radiotherapy transiently reverses tumor education signatures in TAM-MDMImmunology; Systems Biology; Transcriptomics
