ArticleJournal of cancer research and clinical oncology2024
Regulatory T cells inhibit FoxP3 to increase the population of tumor initiating cells in hepatocellular carcinoma.
Article in Journal of cancer research and clinical oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed.
- Autocrine Control of CD276 by SPARC in Liver Cancer and Its Contribution to Immune Escape and Resistance to Immunotherapy: Elucidating How SPARC Shapes the Tumor Microenvironment and Undermines the Response to Immune Checkpoint Inhibition.Journal of biochemical and molecular toxicology · 2026Article
- The Role of CD4Cells · 2026Review
- Exploring the effects of exercise on T cell function and metabolism in cancer: a scoping review protocol.Frontiers in physiology · 2025Article
- Cancer stem cells in hepatocellular carcinoma: therapy resistance and emerging treatments.Frontiers in immunology · 2025Review
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Authors and funding
6 authors.
Funding
Abstract
purposeTumor initiating cells (TICs) or cancer stem cells (CSCs) are considered to be the main culprit of hepatocellular carcinoma (HCC) initiation and progression, nevertheless the mechanism by which tumor microenvironment maintains the HCC 'stemness' is not fully understood. This study aims to investigate the effect of regulatory T cells (Tregs) on the TICs characteristics of HCC.
methodsImmunocytochemistry, flow cytometry, real-time PCR, western blot, in vitro sphere-formation, and in vivo tumorigenesis assay were used to detect HCC 'stemness'. Additionally, after forced expression or inhibition of FoxP3, β-catenin expression and HCC 'stemness' were investigated.
resultsTregs enhanced the 'stemness' of HCC cells by upregulating TIC-related markers CD133, Oct3/4, Sox2, c-Myc, Klf4, Nanog, CD13, EpCAM, and inducting epithelial to mesenchymal transition (EMT), increasing TICs ratio, as well as promoting tumorigenic ability. Moreover, β-catenin and c-Myc were upregulated in HCC cells after co-cultured with Tregs. HCC 'stemness' was inhibited after treatment with Wnt/β-catenin pathway inhibitor. Furthermore, forced expression of FoxP3 resulted in increased GSK3β, decreased β-catenin and TIC ratio in HCC. In contrast, FoxP3 interference reduced GSK3β, enhanced β-catenin and TIC ratio of HCC.
conclusionThis study, for the first time, demonstrated that Tregs increased the population of TICs in HCC by inhibiting FoxP3 as well as promoting β-catenin expression.
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