Nature immunology, 2021-03, Vol.22 (3), p.358-369
- 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
2021
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Details
- Autor(en) / Beteiligte
- 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
- Titel
- IL-2 regulates tumor-reactive CD8 + T cell exhaustion by activating the aryl hydrocarbon receptor
- Ist Teil von
- Nature immunology, 2021-03, Vol.22 (3), p.358-369
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2021
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1529-2908eISSN: 1529-2916DOI: 10.1038/s41590-020-00850-9Titel-ID: cdi_pubmed_primary_33432230
- Format
- –
- Schlagworte
- 5-Hydroxytryptophan - metabolism, Animals, Antibodies, Neutralizing - pharmacology, Antineoplastic Agents - pharmacology, Basic Helix-Loop-Helix Transcription Factors - deficiency, Basic Helix-Loop-Helix Transcription Factors - genetics, Basic Helix-Loop-Helix Transcription Factors - metabolism, CD8-Positive T-Lymphocytes - drug effects, CD8-Positive T-Lymphocytes - immunology, CD8-Positive T-Lymphocytes - metabolism, Gene Expression Regulation, Neoplastic, HCT116 Cells, HEK293 Cells, Humans, Interleukin-2 - antagonists & inhibitors, Interleukin-2 - genetics, Interleukin-2 - metabolism, Jurkat Cells, Lymphocytes, Tumor-Infiltrating - drug effects, Lymphocytes, Tumor-Infiltrating - immunology, Lymphocytes, Tumor-Infiltrating - metabolism, MCF-7 Cells, Melanoma, Experimental - drug therapy, Melanoma, Experimental - immunology, Melanoma, Experimental - metabolism, Melanoma, Experimental - pathology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Neoplasms - drug therapy, Neoplasms - immunology, Neoplasms - metabolism, Neoplasms - pathology, NIH 3T3 Cells, Receptors, Aryl Hydrocarbon - deficiency, Receptors, Aryl Hydrocarbon - genetics, Receptors, Aryl Hydrocarbon - metabolism, Signal Transduction, Tryptophan Hydroxylase - metabolism, Tumor Microenvironment, Xenograft Model Antitumor Assays