Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)771-785
JournalCell
Volume183
Issue number3
DOIs
Publication statusPublished - 29 Oct 2020

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