Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity

2020/10/01 by Lydia Kalafati, Ioannis Kourtzelis, Jonas Schulte-Schrepping +27 · 10 citations
Immunology and Microbiology · #Immune cells in cancer #Immune responses and vaccinations #Immunotherapy and Immune Responses

paper · pdf · doi:10.1016/j.cell.2020.09.058

openalex publication_date 2020/10/01 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

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.

Citations

• Defining trained immunity and its role in health and disease

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