RESTORATION OF TH1/TH2 IMMUNE BALANCE AND CYTOKINE MODULATION IN ORAL SQUAMOUS CELL CARCINOMA: EVIDENCE FROM AN AUTOLOGOUS EX VIVO STUDY USING TRIPHALA

Abstract

Background: Oral squamous cell carcinoma (OSCC) is characterized by tumour-induced immune dysregulation, particularly involving altered cytokine signaling and impaired lymphocyte function. A shift toward a Th2-dominant immunosuppressive environment contributes to tumour progression and therapeutic resistance. Triphala, a traditional polyherbal formulation, has demonstrated immunomodulatory properties; however, its effect on cytokine modulation and immune polarization in OSCC remains inadequately explored. Aim: To evaluate the effect of Triphala on cytokine expression and Th1/Th2 immune polarization in lymphocytes derived from OSCC patients. Materials and Methods: This ex vivo study included forty histopathologically confirmed OSCC patients. Autologous lymphocytes and primary OSCC cells were isolated and cultured. Lymphocytes were treated with increasing concentrations of Triphala (25–500 µg/ml), and cytokine levels (IL-2, TNF-α, IFN-γ, IL-6, and IL-10) were quantified using ELISA in a co-culture system. The Th1/Th2 ratio was calculated to assess immune polarization. Statistical analysis was performed using repeated measures ANOVA with Tukey post hoc test and Pearson correlation analysis. Results: Triphala treatment resulted in significant upregulation of Th1 cytokines (IL-2, TNF-α, IFN-γ) and suppression of IL-6, with a moderate increase in IL-10. This led to a progressive increase in the Th1/Th2 ratio, indicating a shift toward a Th1-dominant immune response. Peak immunomodulatory effects were observed at 300 µg/ml, beyond which a plateau was noted. The increase in Th1/Th2 ratio was associated with reduced tumour cell viability, supporting enhanced immune mediated tumour suppression. Conclusion: Triphala effectively modulates cytokine expression and restores immune balance in OSCC by promoting Th1 polarization. These findings support its potential as an adjunct immunomodulatory agent targeting tumour-associated immune suppression.