Characteristics and prognostic potential of tertiary lymphoid structures in oral tongue squamous cell carcinoma

Recently, tertiary lymphoid structures (TLSs) have been reported in melanoma, NSCLC, breast cancer, colorectal cancer and so on. They are considered to drive local adaptive immune responses against tumors and considered as important sites of extranodal T cell priming and epitope spreading in the responder T cell repertoire. In terms of prognostic value, TLS is the factory for immune response. Therefore TLS act as a favorable clinical outcome for patients. But TLS was seldom reported on oral tongue squamous cell carcinoma. To identify and evaluate the presence of tertiary lymphoid structures in oral tongue squamous cell carcinomas (OTSCC). If present, we would study the prognostic values of TLSs in OTSCC and analyze whether they are related to the survival of OTSCC. The expression of PNAd+ HEV, CD20+ B cells, CD3+ T cells was examined to record the quantity of TLSs, using immunohistochemistry (IHC) in paraffin-embedded tissue samples from 168 OTSCC patients. Overall Survival (OS) and disease-free survival (DFS) were estimated using the Kaplan-Meier method, with a log-rank test. Multivariate survival analysis was done using the Cox proportional hazards model. Variables that were statistically significant in the univariate analysis were entered into multivariate Cox regression analyses to indentify its independent value. TLS was a well-organized structure composed of a specific indicator of HEV and distinct B cell aggregates and T cell area. TLSs were found in about 26.5% of OTSCC patients. Among clinicopathological data [including gender, age, smoking history, alcohol consumption, tumor differentiation, TNM stage and TILs (tumor infiltrating lymphocyte)], TLSs were associated with TILs (p < 0.05). Log-rank test showed that presence of TLS affect the relapse and 5 year overall survival rates of OTSCC (both p < 0.05). In multivariate analyses, TLS was the independent factor of relapse and 5 year overall survival rates of OTSCC (both p < 0.05). The presence of TLS in OTSCC was identified. TLS is associated with adverse prognosis in patients with OTSCC. It may play important roles in preventing the recurrence of OTSCC.