The requisites for protein translation in T cells are poorly understood and how translation shapes the antitumor efficacy of T cells is unknown. Here we demonstrated that IL15-conditioned T cells were primed by the metabolic energy sensor AMP-activated protein kinase to undergo diminished translation relative to effector T cells. However, we showed that IL15-conditioned T cells exhibited a remarkable capacity to enhance their protein translation in tumors, which effector T cells were unable to duplicate. Studying the modulation of translation for applications in cancer immunotherapy revealed that direct ex vivo pharmacologic inhibition of translation elongation primed robust T-cell antitumor immunity. Our work elucidates that altering protein translation in CD8+ T cells can shape their antitumor capability.

中文翻译：

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重塑翻译引发 CD8+ T 细胞抗肿瘤免疫。

T 细胞中蛋白质翻译的必要条件知之甚少，翻译如何影响 T 细胞的抗肿瘤功效尚不清楚。在这里，我们证明了 IL15 条件 T 细胞由代谢能量传感器 AMP 激活的蛋白激酶引发，相对于效应 T 细胞而言，翻译减少。然而，我们发现 IL15 条件 T 细胞表现出显着的能力来增强其在肿瘤中的蛋白质翻译，而效应 T 细胞无法复制。研究在癌症免疫治疗中应用的翻译调节表明，直接体外药理学抑制翻译延伸可引发强大的 T 细胞抗肿瘤免疫。我们的工作阐明了改变 CD8+ T 细胞中的蛋白质翻译可以塑造它们的抗肿瘤能力。