4.7 Article

Regulatory T cells promote glioma cell stemness through TGF-β-NF-κB-IL6-STAT3 signaling

期刊

CANCER IMMUNOLOGY IMMUNOTHERAPY
卷 70, 期 9, 页码 2601-2616

出版社

SPRINGER
DOI: 10.1007/s00262-021-02872-0

关键词

Glioma; Tregs; Glioma stem cell; TGF-beta; Tocilizumab

资金

  1. National Natural Science Foundation of China [91942314, 81771781, 81802857]
  2. National Science and Technology Major Project of China [2020ZX09201-009]

向作者/读者索取更多资源

The intense infiltration of regulatory T cells (Tregs) facilitates the qualities of glioma stem cells (GSCs) through TGF-beta secretion and NF-κB-IL6-STAT3 signaling pathway, leading to increased cancer stemness and tumorigenic potential. Blocking the IL6 receptor can mitigate the promotion effect of Tregs on glioma growth, and the expression levels of CD133, IL6, and TGF-beta could serve as prognosis markers for glioma patients.
Glioma stem cells (GSCs) contribute to the malignant growth of glioma, but little is known about the interaction between GSCs and tumor microenvironment. Here, we found that intense infiltration of regulatory T cells (Tregs) facilitated the qualities of GSCs through TGF-beta secretion that helped coordinately tumor growth. Mechanistic investigations indicated that TGF-beta acted on cancer cells to induce the core cancer stem cell-related genes CD133, SOX2, NESTIN, MUSASHI1 and ALDH1A expression and spheres formation via NF-kappa B-IL6-STAT3 signaling pathway, resulting in the increased cancer stemness and tumorigenic potential. Furthermore, Tregs promoted glioma tumor growth, and this effect could be abrogated with blockade of IL6 receptor by tocilizumab which also demonstrated certain level of therapeutic efficacy in xenograft model. Additionally, expression levels of CD133, IL6 and TGF-beta were found to serve as prognosis markers of glioma patients. Collectively, our findings reveal a new immune-associated mechanism underlying Tregs-induced GSCs. Moreover, efforts to target this network may be an effective strategy for treating glioma.

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