The immune environment of metastatic brain tumors (BrM) remains unknown but is likely to be immunosuppressive with drug resistance. We aimed to determine the immune environment of BrM and the influence of peritumoral astrocytes on it.
Mouse melanoma B16 4A5 was injected into the carotid artery of mice to induce BrM. Finally, the composition of myeloid immune cells in the brain was confirmed by flow cytometry. To recapitulate peritumoral astrocytes in vitro, 2'3'-cyclic AMP-GMP (cGAMP), which is reported to be delivered from BrM to astrocytes and contribute to cancer progression, was introduced directly into astrocytes. The molecular changes downstream of STING signaling that accepts cGAMP were examined. Further, we evaluated the effects of culture supernatants of cGAMP-transfected astrocytes on the migratory ability of neutrophils (derived from HL-60) .
In the brains of BrM, the ratio of neutrophils and macrophages was increased. cGAMP-transfected astrocytes induced and NF-kB target CCL5, and the culture supernatant enhanced HL-60 migration. These results suggest that a specific immune environment is constituted in BrM by mobilizing immune cells of peripheral origin and that astrocyte secretions may be involved.