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.

通过调节成熟的髓样细胞或其骨髓祖细胞而诱导的训练后的先天免疫介导了对继发性挑战的持续增强的反应能力。在这里，我们研究了是否可以通过诱导训练有素的免疫力来增强抗肿瘤免疫力。用β-葡聚糖（一种受过训练的免疫力的真菌衍生的原型激动剂）对小鼠进行预处理，可减少肿瘤的生长。β-葡聚糖诱导的训练免疫的抗肿瘤作用与粒细胞生成的转录组和表观遗传重排以及嗜中性粒细胞重编程为抗肿瘤表型有关。该过程需要I型干扰素信号传导，而与宿主的适应性免疫无关。中性粒细胞从受过β-葡聚糖训练的小鼠过继转移至幼稚受体的过程以ROS依赖性方式抑制了后者的肿瘤生长。此外，β-葡聚糖诱导的训练的粒细胞生成的抗肿瘤作用可通过骨髓移植传递给未接受治疗的小鼠。我们的发现确定了一种经过训练的免疫力，涉及与颗粒细胞生成适当的重新布线有关的新型且与治疗相关的抗肿瘤方面。