Spatial Remodeling of the Immune Microenvironment During Laryngeal Carcinogenesis Reveals Prognostic Immune Patterns in Laryngeal Squamous Cell Carcinoma

Background/Objectives: Despite therapeutic advances, laryngeal squamous cell carcinoma (LSCC) remains a clinical challenge. We investigated immune microenvironment remodeling and its prognostic relevance during laryngeal carcinogenesis.

Methods

This retrospective study included 227 patients: 45 with benign laryngeal polyps, 55 with laryngeal epithelial dysplasia, and 127 with LSCC; 55 (43.3%) LSCCs were Union for International Cancer Control (UICC) stage I–II and 72 (56.7%) stage III–IV. Immunohistochemistry on tissue microarrays (TMAs) was used to assess the density of cluster of differentiation (CD)4-, CD8-, forkhead box P3 (FOXP3)-, programmed cell death protein 1 (PD-1)-, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-, CD68-, and CD163-positive immune cells, together with FOXP3/CTLA-4 double-positive cells. Immune-cell densities were expressed as the percentage of the respective intraepithelial/intratumoral or stromal compartment occupied by positively stained immune cells. An exploratory Protective Immune Score (PIS; 0–2) assigned one point each for high intraepithelial FOXP3 and high stromal CTLA-4 cell density.