PD-L1 Expression in Undifferentiated Nasopharyngeal Carcinoma Is Associated with EBV-LMP1 and Tumor Immune Infiltration : Data from a Tunisian Cohort

Background Programmed death-ligand 1 (PD-L1) is a key immune checkpoint involved in tumor immune evasion and a therapeutic target in immuno-oncology. Undifferentiated nasopharyngeal carcinoma (UCNT) is strongly linked to Epstein–Barr virus (EBV) infection, but data on PD-L1 expression and its relationship with tumor immunity and viral markers in North African populations are limited. Objective To assess PD-L1 expression in UCNT and its associations with clinicopathological features, tumor-infiltrating immune cells, and the viral protein LMP1. Methods We retrospectively analyzed 75 UCNT patients diagnosed at the Salah Azaïez Cancer Institute, Tunis. PD-L1 expression was evaluated by immunohistochemistry using the Tumor Proportion Score (TPS) and Combined Positive Score (CPS). CD8⁺ cytotoxic T cells, FOXP3⁺ regulatory T cells, CD163⁺ macrophages, and LMP1 expression were also assessed. Spearman’s correlation and χ² tests were used, with p < 0.05 considered significant. Results PD-L1 was positive in 70.7% of cases (TPS) and 73.3% (CPS), with strong correlation between the two scores (rho = 0.956 ; p < 0.001). PD-L1 expression was not associated with clinicopathological parameters but showed significant positive correlations with LMP1 (TPS : rho = 0.341; p = 0.003; CPS: rho = 0.345; p = 0.002) and with intratumoral CD8⁺ T cells (rho = 0.371; p = 0.002) and FOXP3⁺ regulatory T cells (rho = 0.253; p = 0.047). No correlation was observed with CD163⁺ macrophages. Conclusion PD-L1 is frequently expressed in UCNT and closely associated with EBV-LMP1 and tumor-infiltrating immune cells. These findings highlight PD-L1 as a potential biomarker and provide insight into the immune-viral interactions shaping the tumor microenvironment in this population.