Suppressive IL-17A(+)Foxp3(+) and ex-Th17 IL-17A(neg)Foxp3(+) T(reg) cells are a source of tumour-associated T(reg) cells.
Suppressive IL-17A(+)Foxp3(+) and ex-Th17 IL-17A(neg)Foxp3(+) T(reg) cells are a source of tumour-associated T(reg) cells.
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DOI：
10.1038/ncomms14649
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发表时间：
2017-03-14
影响因子：
16.6
通讯作者：
Obermajer N
中科院分区：
文献类型：
--
作者：
Downs-Canner S;Berkey S;Delgoffe GM;Edwards RP;Curiel T;Odunsi K;Bartlett DL;Obermajer N
Th17细胞和调节性T细胞（Treg）在维持免疫稳态中不可或缺，并且Th17 - Treg失衡与癌症中的炎症性免疫抑制相关。在此我们表明Th17细胞是肿瘤诱导的Foxp3 +细胞的一个来源。除了从初始前体细胞发育而来的天然（n）Treg细胞和诱导性（i）Treg细胞外，在荷瘤小鼠中，抑制性的IL - 17A + Foxp3 +细胞和ex - Th17 Foxp3 +细胞是从IL - 17A + Foxp3neg细胞转化而来的。表达Foxp3的IL - 17A +细胞、ex - Th17细胞和iTreg细胞的代谢表型显示了表达Foxp3的Treg细胞亚群的代谢适应性和抑制功能之间的分离。尽管所有表达Foxp3的亚群都具有免疫抑制作用，但糖酵解是仅由IL - 17A + Foxp3 +细胞所具有的显著代谢途径。对IL - 17A + Foxp3 +细胞的转录组分析和流式细胞术表明，Folr4、GARP、Itgb8、Pglyrp1、Il1rl1、Itgae、TIGIT和ICOS是Th17向Treg细胞转分化相关的标志物。此处所确定的肿瘤相关的Th17向Treg细胞转化为癌症免疫治疗中靶向Th17 - Treg细胞的动态变化提供了见解。
Th17细胞能够转分化为调节性T细胞（Treg）。在此作者描述了肿瘤驱动的Th17向Treg细胞转分化的特征，并确定了潜在的癌症治疗靶点。
Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17–Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3+ cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A+Foxp3+ and ex-Th17 Foxp3+ cells are converted from IL-17A+Foxp3neg cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A+, ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets. Although all Foxp3-expressing subsets are immunosuppressive, glycolysis is a prominent metabolic pathway exerted only by IL-17A+Foxp3+ cells. Transcriptome analysis and flow cytometry of IL-17A+Foxp3+ cells indicate that Folr4, GARP, Itgb8, Pglyrp1, Il1rl1, Itgae, TIGIT and ICOS are Th17-to-Treg cell transdifferentiation-associated markers. Tumour-associated Th17-to-Treg cell conversion identified here provides insights for targeting the dynamism of Th17–Treg cells in cancer immunotherapy. Th17 cells can transdifferentiate into regulatory T (Treg) cells. Here the authors characterize tumour-driven Th17-to-Treg cell transdifferentiation and identify potential cancer therapy targets.