Abstract
Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. However, the prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear. We used immunohistochemistry to evaluate the presence of tumor-infiltrating FoxP3⁺ T-cells and CTLA-4⁺ cells in four distinct histological compartments (tumor parenchyma and stroma at the tumor center, and parenchyma and stroma at the invasive front) and assessed the association between the prevalence of these cells and the histopathological status of 137 patients with OSCC. Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of FoxP3⁺ T-cells in the parenchyma of the invasive front. Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of CTLA-4⁺ cells in the parenchyma of the invasive front. The presence of FoxP3⁺ T-cells in the parenchyma of the invasive front may be a useful prognostic factor. Our results indicate that FoxP3⁺ T-cells may exert site-specific anti-tumor effects but may not play an immunosuppressive role in OSCC. In addition, our results suggest that CTLA-4+ cells suppress the function of FoxP3+ T-cells and promote anti-tumor immunity in OSCC.
Highlights
Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity and represents more than 90% of oral cancers [1]
Five-year overall survival, disease-specific survival, and recurrence-free survival were favorable in patients with high numbers of Forkhead box protein P3 (FoxP3)+ T-cells in the parenchyma of the invasive front
Recurrence-free survival and metastasis-free survival were decreased in patients with high numbers of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)+ cells in the parenchyma of the invasive front
Summary
Oral squamous cell carcinoma (OSCC) is the most common cancer of the oral cavity and represents more than 90% of oral cancers [1]. Numerous ongoing preclinical and clinical studies have focused on combinational cancer immunotherapy algorithms that are meant to increase treatment efficiency. Despite recent progress in diagnosis and therapy, the prognosis for patients with OSCC remains poor. Patients with higher numbers of inherited defective genes in natural killer (NK) cells were reported to have a higher risk of developing cancer, and inherited defects were associated with tumor immune microenvironment subtypes, recruitment of tumor-infiltrating lymphocytes (TILs), immune checkpoint therapy response, and clinical outcomes [6]. Tumor-infiltrating lymphocytes include tumor-reactive lymphocytes and regulatory T-cells. The prognostic value of tumor-infiltrating lymphocytes in oral squamous cell carcinoma (OSCC) remains unclear
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