Fig. 1.

Regulatory T cells as central modulators of immune dynamics in the tumor microenvironment of OSCC. The tumor microenvironment (TME) of oral squamous cell carcinoma (OSCC) represents a complex immunological landscape where regulatory T cells (Tregs) emerge as critical orchestrators of immunosuppression. Through multiple mechanisms, Tregs effectively suppress anti-tumor immune responses by inhibiting the cytotoxic functions of natural killer (NK) cells and CD8⁺ cytotoxic T lymphocytes (CTLs), while simultaneously suppressing the pro-inflammatory activities of M1 macrophages. By secreting immunosuppressive cytokines, primarily IL-10 and TGF-β, Tregs impair dendritic cell (DC) maturation and antigen presentation, promoting the development of tolerogenic DCs. Additionally, Tregs enhance the immunosuppressive functions of myeloid-derived suppressor cells (MDSCs) and tumor-associated neutrophils (TANs), thereby further inhibiting CTLs responses and contributing to tumor progression. This immunosuppressive network is reinforced by reciprocal interactions between Tregs, M2-polarized macrophages, and regulatory B cells (Bregs), creating self-sustaining circuits that foster tumor immune escape. Cancer-associated fibroblasts (CAFs) contribute by secreting chemokines that recruit Tregs and producing factors that stabilize their function. Additionally, the reduced Th17/Treg ratio observed in OSCC correlates with heightened immune tolerance and advanced disease progression. TME: tumor microenvironment; OSCC: oral squamous cell carcinoma; Treg: regulatory T cell; NK: natural killer; CTL: cytotoxic T lymphocyte; DC: dendritic cell; MDSC: myeloid-derived suppressor cell; TAN: tumor-associated neutrophils; Breg: regulatory B cell; CAF: cancer-associated fibroblast