Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany; National Center for Tumor Diseases, Partner Site Dresden, 01307 Dresden and German Cancer Research Center, Heidelberg, 69120 Heidelberg, Germany.
Institute for Clinical Chemistry and Laboratory Medicine, Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, Germany; National Center for Tumor Diseases, Partner Site Dresden, 01307 Dresden and German Cancer Research Center, Heidelberg, 69120 Heidelberg, Germany; Hull York Medical School, York Biomedical Research Institute, University of York, York, YO10 5DD, UK.
Cell. 2020 Oct 29;183(3):771-785.e12. doi: 10.1016/j.cell.2020.09.058.
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.
经过成熟髓样细胞或其骨髓祖细胞的调节而产生的训练有素的先天免疫介导对二次挑战的持续增强的反应性。在这里，我们研究了是否可以通过诱导训练有素的免疫来增强抗肿瘤免疫。用β-葡聚糖（一种真菌衍生的典型训练免疫激动剂）预处理小鼠会导致肿瘤生长减少。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编程以及向抗肿瘤表型的中性粒细胞重编程有关；该过程需要 I 型干扰素信号传导，而与宿主中的适应性免疫无关。从β-葡聚糖训练的小鼠中过继转移中性粒细胞以依赖 ROS 的方式抑制后者的肿瘤生长。此外，β-葡聚糖诱导的训练性粒细胞生成的抗肿瘤作用可通过骨髓移植传递给受体未成熟的小鼠。我们的发现确定了一种新的、具有治疗相关性的抗肿瘤的训练免疫特征，涉及适当的粒细胞生成重编程。
