CCL19 Suppresses Pancreatic Cancer Progression via Immune Microenvironment Remodeling: Bioinformatics and Functional Insights

This study integrated TCGA data and bioinformatics analysis to identify pivotal regulatory genes and mechanisms within the pancreatic cancer immune microenvironment. A total of 703 immune-related differentially expressed genes (DEGs) were screened, with six hub genes—CCL19, CCR7, CD3G, CXCL19, CXCL13, and FPR1—identified as critical regulators of microenvironment activity. Functional enrichment analysis revealed these genes were prominently involved in immune-related pathways, including T-cell activation and cytokine signaling. Notably, CCL19 exhibited unique immunomodulatory properties: its overexpression showed a significant inverse correlation with pro-tumoral M0 macrophages ( P  < 0.05) and a positive association with anti-tumoral M1 macrophage polarization ( P  < 0.05). In vitro experiments demonstrated that CCL19 overexpression effectively suppressed pancreatic cancer cell proliferation, migration, and invasion, while significantly suppressing tumor growth in mouse xenograft models. Importantly, elevated CCL19 expression correlated with improved patient survival outcomes, suggesting its therapeutic potential in reshaping the tumor immune microenvironment, particularly by promoting macrophage conversion toward an anti-tumoral phenotype. These findings highlight CCL19 as a promising target for immunotherapy in pancreatic cancer.