GSE137762
Cellular and molecular changes of brain metastases-associated myeloid cells during disease progression and therapeutic response
Brain metastasis (BrM) represents a challenging clinical issue. The most common treatment options are surgery and irradiation. Little is known about the complex cellular and molecular microenvironment of BrM, thus lacking molecular targets to combat this dismal disease. It is known that macrophages from the periphery (monocyte-derived macrophages, MDM) and microglia, the brain-resident macrophages, comprise the most abundant stromal cell types in BrM. However, it is not known if both cell types represent a homogeneous cell population with redundant functions or if there are differences due to their ontologic origin. Besides breast cancer and melanoma, the highest incidence of BrM can be found in lung cancer. To gain deeper insight into the myeloid immune landscape, we here provide a resource for the transcriptional landscape of distinct myeloid immune cells associated with lung-to-brain metastasis. Microglia, MDMs, inflammatory monocytes, and granulocytes were FACS-purified from lung-to-brain metastasis at distinct stages following tumor onset and during BrM progression. To evaluate molecular changes due to application of standard therapy, these 4 cell types were also purified at distinct time points upon whole brain radiotherapy of tumor-bearing mice. Additionally, microglia of irradiated mice without BrM were analyzed. Together, our RNA Seq data provide a framework for the identification of molecular targets of the myeloid immune cell landscape in lung cancer BrMs. Overall design: RNA-Seq of FACS purified myeloid cells out of lung-to-brain metastasis (infl. Monocytes, granulocytes, monocyte-derived macrophages, microglia) and their normal cellular counterparts (healthy microglia and peripheral blood monocytes)