Aims Current understanding of oral squamous cell carcinoma (OSCC) is incomplete with regard to prognostic factors that lead to the considerable heterogeneity in treatment response and patient outcomes. We aimed to evaluate the impact of individual tumour-infiltrating lymphocyte (TIL) subsets on prognosis as a possible rationale for this, in a retrospective observational study.

Methods Immunohistochemistry was performed to quantitatively assess cell densities of CD3+, CD20+, CD4+, CD8+ and FOXP3+TIL subsets in 50 surgically treated OSCC cases. Results were correlated with disease-free survival (DFS) and overall survival (OS). Receiver operating characteristic curve analysis and Youden index were applied to determine prognostically significant cut-off values.

Results Mean counts for CD3+, CD4+, CD8+, CD20+ and FOXP3+TILs were 243, 52, 132, 53 and 116 cells per high power field, respectively. High CD8+ and low FOXP3+TIL counts, and high ratio of CD8:FOXP3 were significantly associated with longer DFS and OS, as well as with improved tumour–host interface parameters.

Conclusions Host immune response and its interaction with cancer cells have a significant impact on OSCC outcomes, with some TIL subsets being more clinically relevant than others. High cytotoxic T-cell (CD8) and low Treg (FOXP3) counts, and high cytotoxic T-cell to Treg (CD8:FOXP3) ratio are significantly associated with favourable prognosis. These results may serve as a leading point in identifying novel therapeutic agents that can redesign the tumour immune microenvironment by reducing infiltrating FOXP3-lymphocytes, and modifying their signalling pathways.