Interrelationships Between PD-L1, CTLA-4, IL-10 and IL-18 Expression in Oral Squamous Cell Carcinoma

Oral squamous cell carcinoma (OSCC) is a malignancy characterized by a complex immunosuppressive tumor microenvironment. Immunomodulatory cytokines and immune checkpoints such as PD-L1 (programmed death-ligand 1) and CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) play a crucial role in tumor development. Due to its high mortality rate, OSCC remains one of the major challenges in modern oncology. The aim of this retrospective study was to assess the expression of PD-L1, CTLA-4, IL-10, and IL-18 in paraffin-embedded tumor specimens and to analyze their associations with selected clinicopathological parameters in 79 patients treated surgically between 2011 and 2023. Most patients exhibited intermediate expression of PD-L1 (1-49%; 81.0%), CTLA-4 (1-49%; 87.3%), IL-18 (11-25%; 78.5%), and IL-10 (11-25%; 58.2%). PD-L1 and CTLA-4 expression showed a very strong association (p < 0.001, Cramer's V = 0.823). IL-18 expression was negatively correlated with both PD-L1 (p = 0.017, Cramer's V = 0.322) and CTLA-4 (p = 0.004, Cramer's V = 0.322). A positive correlation between IL-18 and IL-10 expression was also observed (p < 0.001, Cramer's V = 0.403). Among all analyzed biomarkers, only IL-10 expression showed a significant association with 5-year survival in univariate analysis (p = 0.009), with higher IL-10 expression associated with shorter survival. However, this finding did not retain statistical significance in multivariate analysis after adjustment for age and tumor stage. The results indicate a strong relationship between PD-L1 and CTLA-4, suggesting their complementary role in tumor-associated immunosuppression. The observed associations between IL-18 and PD-L1, and between IL-18 and CTLA-4, highlight the complexity of the mechanisms regulating the antitumor immune response. Although IL-10 did not retain independent prognostic significance, the findings from the univariate analysis may indicate a potential role for IL-10 in mechanisms related to tumor progression, warranting further investigation. Future studies should further clarify the interactions between cytokine-related immunoregulatory mechanisms and immune checkpoint pathways in OSCC, particularly in relation to IL-10, IL-18, PD-L1, and CTLA-4 expression.