Infiltration of T cell subsets during oral carcinogenesis

Abstract

Introduction: Alteration of local T cell immune response is often observed in oral squamous cell carcinoma (OSCC). However, their role in premalignant conditions is still unclear. This study has been planned to observe T cell subsets during oral carcinogenesis. Patients and Methods: Cytotoxic, helper, and regulatory T cells infiltrated in tissue of hyperplasia (n = 23), dysplasia (n = 20), and OSCC (n = 100) patients were evaluated by immunohistochemistry and correlated with established clinicopathological parameters and disease status. Results: T cell infiltration was increased in stepwise manner from hyperplasia to dysplasia to carcinoma. Further, in OSCC, high number of T cells was observed in tumor stroma, followed by margin and nest. The ratio of regulatory T cells to cytotoxic and helper T cells was found elevated in tumor nest as compared to tumor stroma and tumor margin. In relation to clinicopathological parameters, significantly low number of cytotoxic T cells in tumor stroma was observed in patients with ≤45 years of age and in Stage III disease as compared to their respective counterparts. Further, significantly low number of helper T cells in tumor stroma and margin was seen in patients with neural invasion as compared to its counterpart. Also, a trend of high number of regulatory T cells in tumor nest and low numbers in stroma and margin was observed in histological Grade III tumors as compared to Grade I and II. Further, a trend of high incidence of disease relapse and death along with reduced disease-free survival was seen in patients with high number of regulatory T cells and elevated regulatory to cytotoxic T cells ratio in tumor nest and stroma. Moreover, an increased regulatory to cytotoxic T cells ratio in dysplasia patients was associated with increased risk for developing squamous cell carcinoma. Conclusion: An altered immune response was in dysplasia and OSCC associated with disease outcome. Regulatory T cells may play a critical role during oral carcinogenesis.