期刊
IMMUNITY INFLAMMATION AND DISEASE
卷 10, 期 11, 页码 -出版社
WILEY
DOI: 10.1002/iid3.727
关键词
CD8(+)T cells; FoxM1; FoxP3; Hilar cholangiocarcinoma; immune escape; Treg cells
类别
This study investigated the mechanism of FoxM1 in immune escape of hilar cholangiocarcinoma (HCCA). The results showed that overexpression of FoxM1 enhanced the inhibitory role of Treg cells in CD8(+) T killing and promoted immune escape of HCCA cells. Moreover, FoxM1 promoted the transcription of FoxP3 by binding to the FoxP3 promoter region. Silencing of FoxP3 neutralized the promoting effect of FoxMl overexpression in Treg cell immunosuppression and HCCA cell immune escape.
Objective: Hilar cholangiocarcinoma (HCCA) is a malignancy related to chronic biliary tract inflammation. Tumor immune escape is a necessary process of tumorigenesis. Forkhead box M1 (FoxM1) could affect the progression of various carcinomas. This study attempted to elaborate on the mechanism of FoxM1 in HCCA immune escape. Methods: HCCA cell lines were collected to measure the expression of FoxM1 and FoxP3. CD8(+) T cells were extracted to establish the co-culture system with HCCA cells and Treg cells. pcDNA3.1-FoxM1 or si-FoxP3 was transfected into HCCA cells in the co-culture system. HCCA cell viability, mobility, and invasiveness as well as levels of transforming growth factor (TGF)-beta and interleukin (IL)-6 were evaluated. The binding relation between FoxM1 and FoxP3 promoter was verified. HCCA cells with pcDNA3.1-FoxM1 were subcutaneously injected into mice to establish the xenograft mouse models. Results: FoxM1 and FoxP3 were overexpressed in HCCA cells. The co-culture of CDS + T and HCCA cells inhibited HCCA cell activity and Treg cells limited CD8(+) T killing. FoxM1 overexpression strengthened the inhibiting role of Treg cells in CD8(+) T killing, upregulated TGF-beta and IL-6 levels, and encouraged HCCA immune escape. FoxM1 bound to the FoxP3 promoter region to promote FoxP3 transcription. Silencing of FoxP3 neutralized the promoting role of FoxMl overexpression in Treg cell immunosuppression and HCCA cell immune escape. FoxMl aggravated tumor development, upregulated FoxP3 expression, increased Treg cells, and reduced CD8(+) T cells. Conclusion: FoxM1 bound to the FoxP3 promoter region to promote FoxP3 transcription and recruited FoxP3(+) Treg cells, thereby inducing HCCA immune escape.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据