Background: Oral Squamous Cell Carcinoma (OSCC) is a significant global health burden, often characterized by aggressive progression and late-stage diagnosis. The tumor microenvironment, particularly the immune response represented by Tumor-Infiltrating Lymphocytes (TILs), plays a crucial role in the host's ability to control neoplastic growth. Understanding how TIL patterns correlate with clinical and pathological features is essential for developing personalized prognostic panels. Objectives: This study aimed to evaluate the infiltration patterns of TILs in patients with OSCC and to analyze their association with clinicopathological variables, life habits, and tumor progression. Methods: An analytical study was conducted including biological samples and clinical data from 115 patients diagnosed with OSCC at a hospital in Southeastern Brazil. Histological sections were stained with Hematoxylin and Eosin (H&E). The TIL pattern was quantified in both the tumor nests (intratumoral) and the surrounding stroma (peritumoral). The infiltration was categorized as high, moderate, or low, based on analysis using a 25x objective lens. Statistical analysis utilized Chi-Square and Fisher's Exact tests, with a significance level of p≤0.05. Results: The cohort was predominantly male (77%), with a mean age of 60 years (range: 32–98). Risk factors included alcohol (50%) and tobacco (47%) consumption, with 42% using both concurrently. The tongue was the most affected site. Most cases were T1/T2 (54%), N0 (54%), and moderately differentiated (57%). Regarding TILs, high counts in both tumor and stroma were significantly associated with smaller primary tumor sizes (T1/T2; p=0.001) and early clinical staging (Stages I/II; p=0.005). Conversely, lower TIL counts were significantly associated with a history of smoking (p=0.026). Conclusions: The findings demonstrate that a robust infiltration of lymphocytes in both the tumor and stroma reflects an active immune response in early-stage OSCC, that may act as a biological barrier against tumor progression. The significantly lower TIL counts observed in smokers suggest that tobacco habits may impair immune defense mechanisms, leading to a suppressed immune profile and potentially more aggressive tumor behavior. Therefore, the standardized assessment of TIL patterns emerges as a highly promising and accessible prognostic tool for risk stratification.

Methodological workflow for the assessment of tumor-infiltrating lymphocytes (TILs) in OSCC patients.