Details

Autor(en) / Beteiligte

• Kalafati, Lydia
• Kourtzelis, Ioannis
• Schulte-Schrepping, Jonas
• Li, Xiaofei
• Hatzioannou, Aikaterini
• Grinenko, Tatyana
• Hagag, Eman
• Sinha, Anupam
• Has, Canan
• Dietz, Sevina
• de Jesus Domingues, Antonio Miguel
• Nati, Marina
• Sormendi, Sundary
• Neuwirth, Ales
• Chatzigeorgiou, Antonios
• Ziogas, Athanasios
• Lesche, Mathias
• Dahl, Andreas
• Henry, Ian
• Subramanian, Pallavi
• Wielockx, Ben
• Murray, Peter
• Mirtschink, Peter
• Chung, Kyoung-Jin
• Schultze, Joachim L.
• Netea, Mihai G.
• Hajishengallis, George
• Verginis, Panayotis
• Mitroulis, Ioannis
• Chavakis, Triantafyllos

Titel

Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

Ist Teil von

• Cell, 2020-10, Vol.183 (3), p.771-785.e12

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2020

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Trained innate immunity, induced via modulation of mature myeloid cells or their bone marrow progenitors, mediates sustained increased responsiveness to secondary challenges. Here, we investigated whether anti-tumor immunity can be enhanced through induction of trained immunity. Pre-treatment of mice with β-glucan, a fungal-derived prototypical agonist of trained immunity, resulted in diminished tumor growth. The anti-tumor effect of β-glucan-induced trained immunity was associated with transcriptomic and epigenetic rewiring of granulopoiesis and neutrophil reprogramming toward an anti-tumor phenotype; this process required type I interferon signaling irrespective of adaptive immunity in the host. Adoptive transfer of neutrophils from β-glucan-trained mice to naive recipients suppressed tumor growth in the latter in a ROS-dependent manner. Moreover, the anti-tumor effect of β-glucan-induced trained granulopoiesis was transmissible by bone marrow transplantation to recipient naive mice. Our findings identify a novel and therapeutically relevant anti-tumor facet of trained immunity involving appropriate rewiring of granulopoiesis. [Display omitted] •Trained innate immunity (TII) promotes anti-tumor activity•TII is linked to transcriptomic and epigenetic rewiring of granulopoiesis•Trained granulopoiesis promotes an anti-tumor phenotype in neutrophils•Trained granulopoiesis might bear potential for cancer immunotherapy Pre-treatment of mice with β-glucan, an agonist of trained immunity responses, leads to epigenetic changes in granulopoiesis and neutrophil function to drive anti-tumor immune responses.