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OBJECTIVE This study was aimed to analyze the role of T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains (TIGIT) expression on T cells in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS Peripheral blood mononuclear cells (PBMC) and tumor-infiltrating lymphocytes (TILs) were collected from OSCC patients. The correlation between TIGIT expression and clinicopathologic features were analyzed by chi-square test. Phenotypic and functional study of TIGIT+ T cells were performed by flow cytometry. RESULTS TIGIT was highly expressed on T cells from PBMC and TILs. High expression of TIGIT on CD4+ T cells (19.0%) and CD8+ T cells (35.9%) was also associated with higher T stage and nodal invasion. Moreover, TIGIT+ CD4+ and TIGIT+ CD8+ T cells sorted from OSCC patients showed a dysfunctional phenotype (low cell proliferation and low secretion of IL-2, TNF-α and IFN-γ), and TIGIT+ CD4+ T cells exhibited inhibitory function (high expression of Foxp3 and high amounts of IL-10). Importantly, TIGIT blockade can enhance the proliferation ability and effective cytokine production (IL-2, TNF-α and IFN-γ) of CD4+ and CD8+ T cells from OSCC patients in vitro. CONCLUSIONS TIGIT-expressing T cells exhibit a lower effector cytokine-releasing phenotype in OSCC patients.