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

Oral Dis. 2021 Oct;27(7):1667-1677. doi: 10.1111/odi.13703. Epub 2020 Nov 19.

Abstract

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.

Keywords: T-cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domains; immune checkpoint molecules; squamous cell carcinoma; tumor microenvironment.

MeSH terms

  • CD8-Positive T-Lymphocytes
  • Carcinoma, Squamous Cell*
  • Head and Neck Neoplasms*
  • Humans
  • Leukocytes, Mononuclear
  • Mouth Neoplasms*
  • Receptors, Immunologic
  • Squamous Cell Carcinoma of Head and Neck

Substances

  • Receptors, Immunologic
  • TIGIT protein, human