Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity.
Innate Immune Training of Granulopoiesis Promotes Anti-tumor Activity.
复制标题
DOI：
10.1016/j.cell.2020.09.058
复制
发表时间：
2020-10-29
期刊：
影响因子：
64.5
通讯作者：
Chavakis T
中科院分区：
文献类型：
--
作者：
Kalafati L;Kourtzelis I;Schulte-Schrepping J;Li X;Hatzioannou A;Grinenko T;Hagag E;Sinha A;Has C;Dietz S;de Jesus Domingues AM;Nati M;Sormendi S;Neuwirth A;Chatzigeorgiou A;Ziogas A;Lesche M;Dahl A;Henry I;Subramanian P;Wielockx B;Murray P;Mirtschink P;Chung KJ;Schultze JL;Netea MG;Hajishengallis G;Verginis P;Mitroulis I;Chavakis T
训练有素的先天免疫，通过调节成熟的髓系细胞或其骨髓祖细胞诱导，调节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性免疫来增强抗肿瘤免疫。用β-葡聚糖(一种真菌衍生的训练免疫的典型激动剂)预治疗小鼠，会导致肿瘤生长减弱。β-葡聚糖诱导的训练性免疫的抗肿瘤作用与粒细胞和中性粒细胞向抗肿瘤表型的转录和表观重排有关；这一过程需要I型干扰素信号，而与宿主的获得性免疫无关。将β-葡聚糖训练的小鼠的中性粒细胞过继转移到幼稚的受者身上，以一种ROS依赖的方式抑制了后者的肿瘤生长。此外，β-葡聚糖诱导的训练性粒系造血的抗肿瘤作用可通过骨髓移植传递给受体幼鼠。我们的发现确定了训练免疫的一个新的和治疗相关的抗肿瘤方面，涉及适当的粒细胞重建。经训练的天然免疫(TII)促进抗肿瘤活性TII与粒细胞的转录和表观重排有关。经训练的粒细胞可促进中性粒细胞的抗肿瘤表型。经训练的粒细胞可能具有抗癌免疫治疗的潜力。用经训练的免疫反应激动剂β-葡聚糖预治疗小鼠，可导致粒细胞和中性粒细胞功能的表观遗传变化，从而驱动抗肿瘤免疫反应。
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. 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 Pre-treatment of mice with β-glucan, an agonist of trained immunity responses, leads to epigenetic changes in granulopoiesis and neutrophil function to drive anti-tumor immune responses.
登录
查看更多内容
影响因子：
30.5
作者：
Chung KJ;Chatzigeorgiou A;Economopoulou M;Garcia-Martin R;Alexaki VI;Mitroulis I;Nati M;Gebler J;Ziemssen T;Goelz SE;Phieler J;Lim JH;Karalis KP;Papayannopoulou T;Blüher M;Hajishengallis G;Chavakis T
通讯作者：
Chavakis T
影响因子：
5.8
作者：
Cheung, NKV;Modak, S;Knuckles, B
通讯作者：
Knuckles, B
影响因子：
15.9
作者：
Alissafi, Themis;Hatzioannou, Aikaterini;Verginis, Panayotis
通讯作者：
Verginis, Panayotis
影响因子：
64.5
作者：
Bekkering, Siroon;Arts, Rob J. W.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
15.9
作者：
Chen, Jianzhou;Cao, Yunhong;Muschel, Ruth J.
通讯作者：
Muschel, Ruth J.