Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF
Key role for neutrophils in radiation-induced antitumor immune responses: Potentiation with G-CSF
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DOI：
10.1073/pnas.1613187113
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发表时间：
2016-10-04
影响因子：
11.1
通讯作者：
Hannan, Raquibul
中科院分区：
文献类型：
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作者：
Takeshima, Tsuguhide;Pop, Laurentiu M.;Hannan, Raquibul
放射治疗（RT）是治疗局部肿瘤的一种主要方式，可以通过被认为涉及免疫系统的远位效应在辐射野外诱导肿瘤消退。我们的研究旨在了解RT在肿瘤微环境中的早期免疫效应，使用几种同基因小鼠肿瘤模型。我们观察到RT诱导无菌性炎症，CD 11b（+）Gr-1（高+）中性粒细胞快速和短暂浸润到肿瘤中。RT募集的肿瘤相关中性粒细胞（RT-Ns）表现出活性氧的产生增加，并诱导肿瘤细胞凋亡。RT-N的肿瘤浸润导致无菌炎症，最终导致肿瘤特异性细胞毒性T细胞的活化，它们被募集到肿瘤部位，以及肿瘤消退。最后，同时给予粒细胞集落刺激因子（G-CSF）通过激活RT-Ns增强RT介导的抗肿瘤活性。我们的研究结果表明，RT和G-CSF的组合应进一步评估在临床前和临床设置。
Radiation therapy (RT), a major modality for treating localized tumors, can induce tumor regression outside the radiation field through an abscopal effect that is thought to involve the immune system. Our studies were designed to understand the early immunological effects of RT in the tumor microenvironment using several syngeneic mouse tumor models. We observed that RT induced sterile inflammation with a rapid and transient infiltration of CD11b(+) Gr-1(high+) neutrophils into the tumors. RT-recruited tumor-associated neutrophils (RT-Ns) exhibited an increased production of reactive oxygen species and induced apoptosis of tumor cells. Tumor infiltration of RT-Ns resulted in sterile inflammation and, eventually, the activation of tumor-specific cytotoxic T cells, their recruitment into the tumor site, and tumor regression. Finally, the concurrent administration of granulocyte colony-stimulating factor (G-CSF) enhanced RT-mediated antitumor activity by activating RT-Ns. Our results suggest that the combination of RT and G-CSF should be further evaluated in preclinical and clinical settings.