Reprogramming of Neutrophils as Non-canonical Antigen Presenting Cells by Radiotherapy-Radiodynamic Therapy to Facilitate Immune-Mediated Tumor Regression
Reprogramming of Neutrophils as Non-canonical Antigen Presenting Cells by Radiotherapy-Radiodynamic Therapy to Facilitate Immune-Mediated Tumor Regression
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DOI：
10.1021/acsnano.1c04363
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发表时间：
2021-11-23
期刊：
影响因子：
17.1
通讯作者：
Lin, Wenbin
中科院分区：
文献类型：
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作者：
Guo, Nining;Ni, Kaiyuan;Lin, Wenbin
肿瘤微环境中无效的抗原交叉呈递损害了抗肿瘤免疫应答的产生。放射治疗-放射动力学疗法（RT-RDT）与纳米级金属有机框架（nMOFs）诱导稳健的适应性免疫应答，尽管典型抗原呈递树突状细胞的适度活化。在这里，使用可移植和自体小鼠肿瘤模型，我们证明了RT-RDT通过早期中性粒细胞浸润和重编程诱导抗肿瘤免疫应答。静脉或瘤内注射nMOFs可募集外周CD 11b（+）Ly 6 G（+）CD 11 c（-）中性粒细胞进入肿瘤。低剂量X射线激活nMOFs显著增加了CD 11b（+）Ly 6 G（+）CD 11 c（+）杂合中性粒细胞的数量，同时上调了共刺激分子CD 80和CD 86以及主要组织相容性复合物II类分子的表达。因此，nMOF激活的RT-RDT通过重编程肿瘤浸润性嗜中性粒细胞以充当非典型抗原呈递细胞来有效交叉呈递肿瘤抗原，从而重塑了有利的肿瘤微环境以用于抗肿瘤免疫应答。
Ineffective antigen cross-presentation in the tumor microenvironment compromises the generation of antitumor immune responses. Radio-therapy-radiodynamic therapy (RT-RDT) with nanoscale metal-organic frameworks (nMOFs) induces robust adaptive immune responses despite modest activation of canonical antigen presenting dendritic cells. Here, using transplantable and autochthonous murine tumor models, we demonstrate that RT-RDT induces antitumor immune responses via early neutrophil infiltration and reprogramming. Intravenous or intratumoral injection of nMOFs recruited peripheral CD11b(+)Ly6G(+)CD11c(-) neutrophils into tumors. The activation of nMOFs by low- dose X- rays significantly increased the population of CD11b(+)Ly6G(+)CD11c(+) hybrid neutrophils with upregulated expression of the co-stimulatory molecules CD80 and CD86 as well as major histocompatibility complex class II molecules. Thus, nMOF-enabled RT-RDT reshapes a favorable tumor microenvironment for antitumor immune responses by reprogramming tumor-infiltrating neutrophils to function as non-canonical antigen presenting cells for effective cross-presentation of tumor antigens.