IL-23 as a potential mediator of immune evasion and therapeutic target in laryngeal squamous cell carcinoma

BACKGROUND: Laryngeal squamous cell carcinoma (LSCC) is a prevalent and aggressive malignancy. Interleukin-23 (IL-23) and its receptor (IL-23R) have been identified as key modulators of the immune response in various cancers, but their role in LSCC remains unclear. This study aimed to examine the expression of IL-23, IL-23R, and FoxP3 + regulatory T cells (Tregs) in LSCC tissues and explore their potential involvement in immune modulation and tumor progression. METHODS: Immunohistochemical staining was performed on 115 LSCC tissue samples to assess the expression of IL-23, IL-23R, and FoxP3 + Tregs. The relationship between IL-23 expression and immune cell infiltration, including CD8 + T cells and Tregs, was analyzed, and survival analysis was conducted. Public datasets (TCGA-HNSC, GSE103322) were utilized for bioinformatic validation. RESULTS: IL-23 was predominantly expressed in tumor cells and stromal immune cells within the TME, while IL-23R was primarily located on immune cells, especially in the invasive margin. IL-23 expression was positively correlated with Treg infiltration and negatively associated with CD8 + T cell density. However, no significant correlation was found between IL-23 expression and overall survival, potentially due to the study’s sample size limitations. Bioinformatic analysis of the TCGA-HNSC cohort confirmed elevated IL23A expression in tumors and revealed its positive correlation with immune infiltration scores, Treg signatures, and enrichment in immune-related pathways. CONCLUSION: IL-23, through its interaction with IL-23R and Tregs, contributes to immune evasion in LSCC. Targeting the IL-23/IL-23R signaling axis may offer a novel therapeutic approach to enhance anti-tumor immunity in LSCC. Larger cohort studies are needed to validate these findings and assess IL-23’s clinical utility as a biomarker and therapeutic target.