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PurposeThe aim of this study was to investigate the prognostic significance of preoperative inflammatory markers in peripheral blood of patients with oral squamous cell carcinoma (OSCC), and to establish correlations with the infiltrate of macrophages and lymphocytes in the local immune tumor microenvironment (TME).Materials and MethodsNeutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), lymphocyte-monocyte ratio (LMR), and systemic immune-inflammation index (SII) were retrospectively evaluated in a cohort of 348 OSCC patients, and correlated with overall (OS) and disease-specific survival (DSS). Immunohistochemical analysis of tumoral and stromal infiltration of CD8+, CD4+, FOXP3+ and CD20+ lymphocytes and CD68+ and CD163+ macrophages was performed in a subset of 119 OSCC patient samples, and correlations further assessed.ResultsNLR, SII, and LMR were significantly associated with a poorer OS in univariate analysis; however, only NLR remained a significant independent predictor in the multivariate analysis (HR = 1.626, p = 0.04). NLR and SII were inversely and significantly correlated with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes. Moreover, a significant correlation between LMR was also found to significantly associate with stromal infiltration of CD8+, CD4+, and CD20+ lymphocytes, stromal CD68+ and CD163+ macrophages, and also tumoral infiltration of CD4+ and CD20+ lymphocytes.ConclusionsPreoperative NLR, SII, and LMR may serve as valuable systemic markers to predict OSCC patient survival, with NLR emerging as an independent predictor of poor OS. Moreover, strong significant correlations were exclusively observed between systemic inflammatory markers and the local stromal infiltration of lymphocytes in the TME.