Unveiling the power of plumbagin: revitalizing exhausted T cells to combat tongue cancer
Abstract 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...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-07-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-025-03892-x |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | Abstract 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. Graphical Abstract Image created with Figdraw.com, with permission |
|---|---|
| ISSN: | 1475-2867 |