Restored Thymic Output after Androgen Blockade Participates in Antitumor Immunity.

Restored Thymic Output after Androgen Blockade Participates in Antitumor Immunity.
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DOI:
10.4049/jimmunol.2200696
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发表时间:
2023-02-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Moran AE
Moran AE
中科院分区:
其他
文献类型:
--
作者:
Polesso F;Caruso B;Hammond SA;Moran AE

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胸腺是一种激素敏感器官,它会随着年龄的增长而退化,以响应性类固醇的产生。胸腺退化导致近期胸腺移民(RTE)的产生减少,从而导致对癌症等免疫挑战的反应减弱。有趣的是,前列腺癌患者的标准治疗是雄激素剥夺疗法,这会导致胸腺再生和胸腺输出增加。目前尚不清楚这些新产生的 T 细胞是否有助于抗肿瘤免疫反应。本研究定义了小鼠胸腺再生响应 ADT 的动力学,确定胸腺上皮细胞 (TEC) 增殖对于 RTE 输出的增加至关重要。使用一种新的小鼠模型来追踪体内 RTE,我们证明这些新产生的 RTE 可以运输到肿瘤,在那里它们被激活并产生与更成熟的 T 细胞相似的水平的效应细胞因子。总的来说,这些数据表明 ADT 诱导的胸腺再生产生的 RTE 可用于抗肿瘤免疫反应。
The thymus is a hormone sensitive organ, which involutes with age in response to production of sex steroids. Thymic involution leads to a decrease in the generation of recent thymic emigrants (RTE), resulting in a reduced response to immune challenges such as cancer. Interestingly, the standard of care for prostate cancer patients is androgen deprivation therapy, which leads to thymic regeneration and an increase in thymic output. It remains unknown whether these newly produced T cells can contribute to the anti-tumor immne response. The present study defines the kinetics of thymic regeneration in response to ADT in mice, determining that thymic epithelial cell (TEC) proliferation is critical for the increase in RTE output. Using a novel mouse model to track RTE in vivo, we demonstrate that these newly generated RTE can traffic to tumors where they become activated and produce effector cytokines at levels similar to more mature T cells. Collectively, these data suggest that RTE produced from ADT-induced thymic regeneration could be harnessed for the anti-tumor immune response.
DOI: 10.1098/rspb.1974.0056
发表时间: 1974-01-01
期刊: PROCEEDINGS OF THE ROYAL SOCIETY SERIES B-BIOLOGICAL SCIENCES
影响因子: --
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