| Autor: |
Liu, Yuying, Zhou, Nannan, Zhou, Li, Wang, Jing, Zhou, Yabo, Zhang, Tianzhen, Fang, Yi, Deng, Jinwei, Gao, Yunfeng, Liang, Xiaoyu, Lv, Jiadi, Wang, Zhenfeng, Xie, Jing, Xue, Yuanbo, Zhang, Huafeng, Ma, Jingwei, Tang, Ke, Fang, Yiliang, Cheng, Feiran, Zhang, Chengjuan, Dong, Bing, Zhao, Yuzhou, Yuan, Peng, Gao, Quanli, Zhang, Haizeng, Xiao-Feng Qin, F., Huang, Bo |
| Zdroj: |
Nature Immunology; March 2021, Vol. 22 Issue: 3 p358-369, 12p |
| Abstrakt: |
CD8+T cell exhaustion dampens antitumor immunity. Although several transcription factors have been identified that regulate T cell exhaustion, the molecular mechanisms by which CD8+T cells are triggered to enter an exhausted state remain unclear. Here, we show that interleukin-2 (IL-2) acts as an environmental cue to induce CD8+T cell exhaustion within tumor microenvironments. We find that a continuously high level of IL-2 leads to the persistent activation of STAT5 in CD8+T cells, which in turn induces strong expression of tryptophan hydroxylase 1, thus catalyzing the conversion to tryptophan to 5-hydroxytryptophan (5-HTP). 5-HTP subsequently activates AhR nuclear translocation, causing a coordinated upregulation of inhibitory receptors and downregulation of cytokine and effector-molecule production, thereby rendering T cells dysfunctional in the tumor microenvironment. This molecular pathway is not only present in mouse tumor models but is also observed in people with cancer, identifying IL-2 as a novel inducer of T cell exhaustion. |
| Databáze: |
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