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.

脓毒症会引起免疫改变，这种改变会在疾病消退后持续数月。这种免疫重编程对患癌症风险的影响尚不清楚。在这里，我们使用一个国家索赔数据库来显示败血症幸存者的癌症累积发病率低于匹配的非严重感染幸存者。我们确定了从脓毒症训练的驻留巨噬细胞释放的趋化因子网络，该网络通过 CCR2 和 CXCR6 刺激触发 T 细胞的组织驻留，作为免疫机制，导致脓毒症治愈后肿瘤从头发展的风险降低。虽然非脓毒症炎症不会引发该网络，但昆布多糖注射可以在治疗上重现脓毒症的保护作用。在脓毒症患者中检测到这种趋化因子网络和 CXCR6 组织驻留 T 细胞积聚，并且与癌症患者的生存期延长相关。这些发现确定了脓毒症诱导的训练有素的免疫力具有治疗相关的抗肿瘤结果。