法国国家健康与医学研究院Antoine Roquilly等研究人员合作发现，败血症训练的巨噬细胞可促进抗肿瘤组织驻留T细胞的生成。这一研究成果于2024年4月29日在线发表在国际学术期刊《自然—免疫学》上。

研究人员利用全国索赔数据库表明，与匹配的非严重感染幸存者相比，败血症幸存者的癌症累积发病率较低。研究人员发现，脓毒症训练的常驻巨噬细胞释放的趋化因子网络，通过CCR2和CXCR6的刺激触发T细胞的组织驻留，这是败血症治愈后降低新发肿瘤风险的免疫机制。虽然非败血症炎症不会引发这种网络，但注射海带多糖可以治疗性地再现败血症的保护作用。

这种趋化因子网络和CXCR6组织驻留T细胞的积累在败血症患者中被检测到，并且与癌症患者的生存期延长有关。这些发现确定了败血症诱导的训练免疫对抗肿瘤的治疗作用。

据悉，败血症会诱发免疫改变，这种改变在病愈后会持续数月。这种免疫学重编程对癌症发病风险的影响尚不清楚。

附：英文原文

Title: Sepsis-trained macrophages promote antitumoral tissue-resident T cells

Author: Broquet, Alexis, Gourain, Victor, Goronflot, Thomas, Le Mabecque, Virginie, Sinha, Debajyoti, Ashayeripanah, Mitra, Jacqueline, Cdric, Martin, Pierre, Davieau, Marion, Boutin, Lea, Poulain, Cecile, Martin, Florian P., Fourgeux, Cynthia, Petrier, Melanie, Cannevet, Manon, Leclercq, Thomas, Guillonneau, Maeva, Chaumette, Tanguy, Laurent, Thomas, Harly, Christelle, Scotet, Emmanuel, Legentil, Laurent, Ferrires, Vincent, Corgnac, Stephanie, Mami-Chouaib, Fathia, Mosnier, Jean Francois, Mauduit, Nicolas, McWilliam, Hamish E. G., Villadangos, Jose A., Gourraud, Pierre Antoine, Asehnoune, Karim, Poschmann, Jeremie, Roquilly, Antoine

Issue&Volume: 2024-04-29

Abstract: 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.

DOI: 10.1038/s41590-024-01819-8

Source: https://www.nature.com/articles/s41590-024-01819-8