Thursday Seminar–>17h : Mikala Egeblad (by Zoom)

Title: “NETworking in cancer: bidirectional interplay between neutrophils and tumors drives metastasis” Abstract: Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients. Yet, the reasons for these associations are unclear. We show that chronic stress increased lung metastasis from disseminated cancer cells 2-4-fold in mice. Chronic stress significantly altered the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolished the stress-induced metastasis, indicating neutrophils’ critical role. Chronic stress shifted the normal circadian rhythm of neutrophils and, via glucocorticoids release, caused increased neutrophil extracellular trap (NET) formation. Importantly, in mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress failed to increase NET levels and metastasis. Furthermore, digesting NETs with deoxyribonuclease (DNase) I prevented chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause the formation of NETs and establishment of a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.