Sepsis-trained macrophages promote antitumoral tissue-resident T cells

Menée à partir notamment de données portant sur 55 234 patients ayant survécu à un sepsis et sur 87 164 patients ayant présenté une inflammation aseptique, cette étude met en évidence l'effet protecteur d'un sepsis contre le développement tumoral et identifie son mécanisme biologique

Résumé en anglais

Sepsis induces immune alterations, which last for months after the resolution of illness. The effect of this immunological reprogramming on the risk of developing cancer is unclear. Here we use a national claims database to show that sepsis survivors had a lower cumulative incidence of cancers than matched nonsevere infection survivors. We identify a chemokine network released from sepsis-trained resident macrophages that triggers tissue residency of T cells via CCR2 and CXCR6 stimulations as the immune mechanism responsible for this decreased risk of de novo tumor development after sepsis cure. While nonseptic inflammation does not provoke this network, laminarin injection could therapeutically reproduce the protective sepsis effect. This chemokine network and CXCR6 tissue-resident T cell accumulation were detected in humans with sepsis and were associated with prolonged survival in humans with cancer. These findings identify a therapeutically relevant antitumor consequence of sepsis-induced trained immunity.