Cell, Developmental and Cancer Biology, Oregon Health and Science University, Portland, OR.
Discovery Biosciences, R&D Oncology, AstraZeneca, Gaithersburg, MD; and.
J Immunol. 2023 Feb 15;210(4):496-503. doi: 10.4049/jimmunol.2200696.
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 (RTEs), resulting in a reduced response to immune challenges such as cancer. Interestingly, the standard of care for prostate cancer patients is androgen deprivation therapy (ADT), which leads to thymic regeneration and an increase in thymic output. It remains unknown whether these newly produced T cells can contribute to the antitumor immune response. This study defines the kinetics of thymic regeneration in response to ADT in mice, determining that thymic epithelial cell proliferation is critical for the increase in RTE output. Using a mouse model to track RTE in vivo, we demonstrate that these newly generated RTEs 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 RTEs produced from ADT-induced thymic regeneration could be harnessed for the antitumor immune response.
胸腺是一种对激素敏感的器官，随着年龄的增长，它会对性激素的产生产生反应而发生退化。胸腺退化导致新近产生的胸腺迁出细胞（RTE）的生成减少，从而导致对免疫挑战（如癌症）的反应减弱。有趣的是，前列腺癌患者的标准治疗方法是雄激素剥夺疗法（ADT），它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 细胞是否能有助于抗肿瘤免疫反应。本研究定义了 ADT 治疗后小鼠胸腺再生的动力学，确定胸腺上皮细胞增殖对于 RTE 输出的增加至关重要。通过使用一种追踪体内 RTE 的小鼠模型，我们证明这些新产生的 RTE 可以迁移到肿瘤中，在那里它们被激活并产生与更成熟 T 细胞相似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。
