【《Nature Metabolism》——T细胞免疫治疗的潜在靶点：戊二酸】
研究人员揭示了戊二酸作为CD8+T细胞代谢和细胞毒性的调节剂的潜在核心作用。研究结果表明戊二酸是T细胞代谢和分化的重要调节因子，在改善T细胞免疫治疗中具有潜在作用。

【题目】戊二酸调节T细胞代谢和抗肿瘤免疫

【摘要】T细胞功能和细胞周期会受到多种氨基酸分解代谢产物的影响：在某些情况下，代谢产物通过对α-酮戊二酸依赖性双加氧酶的酶促抑制发挥作用，在另一些情况下，代谢产物通过对重要靶点的赖氨酸翻译后修饰发挥作用。我们在研究中发现，氨基酸分解代谢的产物戊二酸两种情况都有参与，并且会对T细胞的功能和分化产生极大影响。我们发现戊二酸通过抑制α-酮戊二酸依赖性双加氧酶，以及通过丙酮酸脱氢酶E2亚单位的戊二化直接调节T细胞代谢来发挥作用。小鼠体内给药戊二酸二乙酯（DEG，戊二酸的一种细胞通透形式）可改变CD8+T细胞分化，并增加对靶细胞的细胞毒性。研究结果显示体内给药DEG与外周和瘤内细胞毒性CD8+T细胞的水平增加相关。这些结果表明戊二酸是T细胞代谢和分化的重要调节因子，在改善T细胞免疫治疗中具有潜在作用。

英文原文

[Report] Researchers revealed a potentially central role for glutarate as a modulator and regulator of CD8+T cell metabolism and cytotoxicity. The study results demonstrate that glutarate is an important regulator of T cell metabolism and differentiation with a potential role in the improvement of T cell immunotherapy.

[Title] Glutarate regulates T cell metabolism and anti-tumour immunity
[Authors] Eleanor Minogue, Pedro P. Cunha, Brennan J. Wadsworth, Guinevere L. Grice, Shiv K. Sah-Teli, Rob Hughes, David Bargiela, Alessandro Quaranta, Javier Zurita, Robin Antrobus, Pedro Velica, Laura Barbieri, Craig E. Wheelock, Peppi Koivunen, James A. Nathan, Iosifina P. Foskolou & Randall S. Johnson

[Abstract] T cell function and fate can be influenced by several metabolites: in some cases, acting through enzymatic inhibition of α-ketoglutarate-dependent dioxygenases, in others, through post-translational modification of lysines in important targets. We show here that glutarate, a product of amino acid catabolism, has the capacity to do both, and has potent effects on T cell function and differentiation. We found that glutarate exerts those effects both through α-ketoglutarate-dependent dioxygenase inhibition, and through direct regulation of T cell metabolism via glutarylation of the pyruvate dehydrogenase E2 subunit. Administration of diethyl glutarate, a cell-permeable form of glutarate, alters CD8+ T cell differentiation and increases cytotoxicity against target cells. In vivo administration of the compound is correlated with increased levels of both peripheral and intratumoural cytotoxic CD8+ T cells. These results demonstrate that glutarate is an important regulator of T cell metabolism and differentiation with a potential role in the improvement of T cell immunotherapy.

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