FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
In: Nature Communications, Jg. 15 (2024), Heft 1, S. 1-16
Online
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Zugriff:
Abstract 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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FOXP3+ regulatory T cell perturbation mediated by the IFNγ-STAT1-IFITM3 feedback loop is essential for anti-tumor immunity
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Autor/in / Beteiligte Person: | 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 |
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Zeitschrift: | Nature Communications, Jg. 15 (2024), Heft 1, S. 1-16 |
Veröffentlichung: | Nature Portfolio, 2024 |
Medientyp: | academicJournal |
ISSN: | 2041-1723 (print) |
DOI: | 10.1038/s41467-023-44391-9 |
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