Prognostic Relevance of CD4, CD8 and FOXP3 TILs in Oral Squamous Cell Carcinoma and Correlations with PD-L1 and Cancer Stem Cell Markers.

This study investigates the relevance of tumor-infiltrating lymphocytes (TILs) in oral squamous cell carcinoma (OSCC). Immunohistochemical analysis of stromal/tumoral CD4, CD8 and FOXP3 TILs is performed in 125 OSCC patients. Potential relationships with the expression of tumoral PD-L1 and cancer stem cell (CSC) markers (NANOG, SOX2, OCT4, Nestin and Podoplanin (PDPN)) are assessed. CD4 and CD8 TILs are significantly associated with smoking and alcohol habits. CD4 and CD8 TILs show an inverse relationship with NANOG and SOX2 expression, and FOXP3 TILs is significantly correlated with Nestin and PDPN expression. High infiltration of CD4 and CD8 TILs and a high tumoral CD8/FOXP3 ratio are significantly associated with tumors harboring positive PD-L1 expression. Infiltration of stromal/tumoral FOXP3 TILs and a low stromal CD8/FOXP3 ratio are significantly associated with better disease-specific survival. Multivariate analysis reveals that the stromal CD8/FOXP3 TILs ratio is a significant independent prognostic factor. Regarding OSCC patient survival, the CD8/FOXP3 TILs ratio is an independent prognostic factor. TILs may act as biomarkers and potential therapeutic targets for OSCC.