Dysfunctional role of elevated TIGIT expression on T cells in oral squamous cell carcinoma patients

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 was 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.