ArticleInfectious agents and cancer2026
CD44 expression associates with EBV LMP1, reduced CD8⁺ T cell infiltration, and lower PD-L1 combined positive score in nasopharyngeal carcinoma.
Article in Infectious agents and cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundNasopharyngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy characterized by a highly immune-infiltrated yet clinically heterogeneous tumor microenvironment. Iron metabolism has been proposed as a potential determinant of tumor progression and immune regulation. CD44 and transferrin receptor 1 (TfR1) represent two distinct iron uptake pathways, but their relative contribution to EBV-driven NPC and immune modulation remains unclear.
methodsSixty-eight NPC biopsies from a Tunisian cohort were analyzed by immunohistochemistry for CD44, TfR1, EBV LMP1, PD-L1, CD8, FoxP3, and CD163. Associations with clinicopathological parameters and immune infiltrates were assessed using chi-square and Spearman correlation tests.
resultsHigh CD44 expression was observed in 48.5% of cases and was significantly associated with lymph node involvement (p = 0.012) and TNM stage (p = 0.042). CD44 expression positively correlated with LMP1 (r = 0.463, p = 0.001). In contrast, CD44 was inversely correlated with CD8⁺ T-cell infiltration (r = - 0.283, p = 0.019) and PD-L1 combined positive score (CPS) (r = - 0.247, p = 0.042). A significant positive correlation was observed between LMP1 and PD-L1 expression, both for tumor proportion score (TPS) (r = 0.341, p = 0.003) and CPS (r = 0.345, p = 0.002). In contrast, TfR1 expression was associated with advanced tumor stage (p = 0.022) but showed no significant relationship with immune parameters or LMP1. CD44 and TfR1 expression were inversely correlated (r = - 0.250, p = 0.040), suggesting alternative iron acquisition pathways.
conclusionOur findings suggest that CD44 may act as a key regulator linking iron metabolism and immune modulation in EBV-associated NPC. Although direct iron measurements were not performed, the observed associations with reduced CD8⁺ T-cell infiltration are consistent with a potential role of CD44 in shaping an immune-restricted tumor microenvironment. These results provide integrative evidence of a CD44-iron-immune axis in a Tunisian NPC cohort and highlight CD44 as a potential prognostic biomarker and therapeutic target.
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