PD-L1 Expression and Immune Microenvironment Remodeling During Laryngeal Carcinogenesis: Implications for Malignant Progression of Laryngeal Dysplasia

Laryngeal dysplasia (LD) is the principal precursor of laryngeal squamous cell carcinoma (LSCC), but reliable biomarkers predicting malignant transformation remain unavailable. This study investigated programmed death-ligand 1 (PD-L1) expression and immune microenvironment remodeling during laryngeal carcinogenesis. Immunohistochemical analysis of PD-L1, CD4, CD8, CD68, and CD163 was performed in 36 benign lesions, 41 LDs, and 102 LSCCs. PD-L1 expression was assessed using the combined positive score (CPS) and tumor proportion score (TPS), while immune cell infiltration was quantified in the intraepithelial and stromal compartments and across the entire tissue specimen. PD-L1 expression and infiltration of all investigated immune cell populations increased progressively from benign lesions through dysplasia to invasive carcinoma. High-grade dysplasia exhibited significantly greater CD4 infiltration in all compartments and increased stromal CD8 and CD163 infiltration than low-grade dysplasia. PD-L1 expression positively correlated with intraepithelial CD163 and stromal CD8 infiltration. Although no biomarker independently distinguished progressive from non-progressive dysplasia, overall CD4, intraepithelial and overall CD68, and stromal CD163 were associated with progression risk. Immune microenvironment remodeling begins during the dysplastic stage of laryngeal carcinogenesis. These findings may improve risk stratification of laryngeal dysplasia and support the development of immunopreventive and immune-targeted therapeutic strategies.