دورية أكاديمية
FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
| العنوان: | FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity |
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| المؤلفون: | Liu, Xinnan, Zhang, Weiqi, Han, Yichao, Cheng, Hao, Liu, Qi, Ke, Shouyu, Zhu, Fangming, Lu, Ying, Dai, Xin, Wang, Chuan, Huang, Gonghua, Su, Bing, Zou, Qiang, Li, Huabing, Zhao, Wenyi, Xiao, Lianbo, Lu, Linrong, Tong, Xuemei, Pan, Fan, Li, Hecheng, Li, Bin |
| المساهمون: | National Natural Science Foundation of China |
| المصدر: | Nature Communications ; volume 15, issue 1 ; ISSN 2041-1723 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary |
| الوصف: | 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. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1038/s41467-023-44391-9 |
| الإتاحة: | https://doi.org/10.1038/s41467-023-44391-9Test https://www.nature.com/articles/s41467-023-44391-9.pdfTest https://www.nature.com/articles/s41467-023-44391-9Test |
| حقوق: | https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: | edsbas.A3E4E31D |
| قاعدة البيانات: | BASE |
| DOI: | 10.1038/s41467-023-44391-9 |
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