Cancer cell international · 2025
Unveiling the power of plumbagin: revitalizing exhausted T cells to combat tongue cancer.
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Zhang Rongrong, Jiang Qingkun, Guo Runying, Guo Ke, Qiu Jiaxuan
Аннотация
BACKGROUND: Tongue squamous cell carcinoma (TSCC), the most common form of oral cancer, has a poor prognosis associated with immune escape due to T cell exhaustion within the tumor microenvironment (TME). Numerous studies have demonstrated the anticancer properties of plumbagin; however, the correlation between plumbagin and TME-immune escape is unknown. This study aimed to evaluate the immunomodulatory effects of plumbagin in TSCC to facilitate the development of neoadjuvant immunotherapy strategies.
METHODS: We stimulated T cells with an antigen to induce a decrease in their cytotoxic function, an increase in programmed cell death-1(PD-1) expression, and exhaustion. Subsequently, plumbagin was utilized to target exhausted T cells, and its effect was evaluated using flow cytometry of apoptosis and PD-1 expression. Furthermore, a quantitative reverse transcription polymerase chain reaction measured the expression of immunoenhancing cytokines (Granzyme B, IFN-γ) and immunosuppressive cytokines (IL-10 and TGF-β). In vivo, plumbagin-treated homograft tongue cancer mouse and in situ tongue cancer model showed alterations in T cells, PD-1 expression and cytokines using flow cytometry and immunohistochemistry.
RESULTS: We found that plumbagin enhances the viability of exhausted T cells in vitro, enhancing apoptosis and decreasing PD-1 expression. In vivo, plumbagin inhibits TSCC growth, increases CD8+ T/CD4+ T cell ratio and decreases Treg cells and expression of PD-1. Furthermore, the expression of cytokines were regulated within the tumor.
CONCLUSIONS: Plumbagin restores exhausted T cells'viability via multiple PD-L1/PD-1 axis, inhibiting TSCC immune escape and providing a theoretical foundation for immune microenvironment regulation.
METHODS: We stimulated T cells with an antigen to induce a decrease in their cytotoxic function, an increase in programmed cell death-1(PD-1) expression, and exhaustion. Subsequently, plumbagin was utilized to target exhausted T cells, and its effect was evaluated using flow cytometry of apoptosis and PD-1 expression. Furthermore, a quantitative reverse transcription polymerase chain reaction measured the expression of immunoenhancing cytokines (Granzyme B, IFN-γ) and immunosuppressive cytokines (IL-10 and TGF-β). In vivo, plumbagin-treated homograft tongue cancer mouse and in situ tongue cancer model showed alterations in T cells, PD-1 expression and cytokines using flow cytometry and immunohistochemistry.
RESULTS: We found that plumbagin enhances the viability of exhausted T cells in vitro, enhancing apoptosis and decreasing PD-1 expression. In vivo, plumbagin inhibits TSCC growth, increases CD8+ T/CD4+ T cell ratio and decreases Treg cells and expression of PD-1. Furthermore, the expression of cytokines were regulated within the tumor.
CONCLUSIONS: Plumbagin restores exhausted T cells'viability via multiple PD-L1/PD-1 axis, inhibiting TSCC immune escape and providing a theoretical foundation for immune microenvironment regulation.