"training" the innate immune system with β-glucan, a compound derived from fungus, inspired the production of innate immune cells, specifically neutrophils, that were primed to prevent or attack tumors in an animal model.
β-glucan is already in clinical trials for cancer immunotherapy, but the researchers say this finding suggests a novel mechanism of action with new treatment approaches.
"This is a breakthrough concept that can be therapeutically exploited for cancer immunotherapy in humans," Hajishengallis says, "specifically by transferring neutrophils from β-glucan-trained donors to cancer patients who would be recipients."
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
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-trainedmice 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.