Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth
Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth
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DOI：
10.1073/pnas.1720113115
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发表时间：
2018-07-10
影响因子：
11.1
通讯作者：
Piconese, Silvia
中科院分区：
文献类型：
--
作者：
Pacella, Ilenia;Procaccini, Claudio;Piconese, Silvia
肿瘤微环境抑制常规T细胞（Tconv）活化，同时促进Tconv扩增。在这里，我们表明，在肿瘤环境中的THBE的优势依赖于补充能量途径，涉及脂质代谢。在小鼠模型中，肿瘤浸润性THBE显示细胞内脂质蓄积，这可归因于脂肪酸（FA）合成速率增加。由于葡萄糖摄取的相对优势可能会在肿瘤内Tcells中促进FA合成，因此我们证明了糖酵解和氧化代谢都有助于Tcells的扩增。我们证实了我们在人类肿瘤中的数据，表明TdR显示了一个面向糖酵解和脂质合成的基因签名。我们的数据支持一种模型，其中来自肿瘤微环境的信号诱导糖酵解、FA合成和氧化的回路，该回路赋予TdR优先增殖优势，其靶向可能代表癌症治疗的策略。
The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment.