FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
© 2024. The Author(s)..
Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature communications - 15(2024), 1 vom: 02. Jan., Seite 122 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Liu, Xinnan [VerfasserIn] |
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| Links: |
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| Themen: |
Cytokines |
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| Anmerkungen: |
Date Completed 05.01.2024 Date Revised 05.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41467-023-44391-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366584901 |
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| 245 | 1 | 0 | |a FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity |
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| 520 | |a © 2024. The Author(s). | ||
| 520 | |a Targeting tumor-infiltrating regulatory T cells (Tregs) is an efficient way to evoke an anti-tumor immune response. However, how Tregs maintain their fragility and stability remains largely unknown. IFITM3 and STAT1 are interferon-induced genes that play a positive role in the progression of tumors. Here, we showed that IFITM3-deficient Tregs blunted tumor growth by strengthening the tumor-killing response and displayed the Th1-like Treg phenotype with higher secretion of IFNγ. Mechanistically, depletion of IFITM3 enhances the translation and phosphorylation of STAT1. On the contrary, the decreased IFITM3 expression in STAT1-deficient Tregs indicates that STAT1 conversely regulates the expression of IFITM3 to form a feedback loop. Blocking the inflammatory cytokine IFNγ or directly depleting STAT1-IFITM3 axis phenocopies the restored suppressive function of tumor-infiltrating Tregs in the tumor model. Overall, our study demonstrates that the perturbation of tumor-infiltrating Tregs through the IFNγ-IFITM3-STAT1 feedback loop is essential for anti-tumor immunity and constitutes a targetable vulnerability of cancer immunotherapy | ||
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| 700 | 1 | |a Zhang, Weiqi |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Yichao |e verfasserin |4 aut | |
| 700 | 1 | |a Cheng, Hao |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Qi |e verfasserin |4 aut | |
| 700 | 1 | |a Ke, Shouyu |e verfasserin |4 aut | |
| 700 | 1 | |a Zhu, Fangming |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Dai, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Chuan |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Gonghua |e verfasserin |4 aut | |
| 700 | 1 | |a Su, Bing |e verfasserin |4 aut | |
| 700 | 1 | |a Zou, Qiang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Huabing |e verfasserin |4 aut | |
| 700 | 1 | |a Zhao, Wenyi |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Lianbo |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Linrong |e verfasserin |4 aut | |
| 700 | 1 | |a Tong, Xuemei |e verfasserin |4 aut | |
| 700 | 1 | |a Pan, Fan |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Hecheng |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Bin |e verfasserin |4 aut | |
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