B3GNT3 overexpression promotes tumor progression and inhibits infiltration of CD8+ T cells in pancreatic cancer

Abstract

Beta-1,3-<i>N</i>-acetylglucosaminyltransferase 3 (<i>B3GNT3</i>) has been associated with tumor progression in several solid tumors, and inhibits CD8⁺ T cell-mediated anti-tumor immunity in breast cancer. However, little is known about the potential functions of <i>B3GNT3</i> in immunosuppression in pancreatic cancer (PC). This study on <i>B3GNT3</i> aims to provide novel insights into the mechanisms of immune suppression or evasion in PC. To this end, the clinical significance and oncologic roles of <i>B3GNT3</i> were investigated through bioinformatic analysis and <i>in vitro</i> studies. Potential associations between the expression of <i>B3GNT3</i> and tumor immunity were mainly analyzed by single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence in tissue microarray (TMA). <i>B3GNT3</i> overexpression was observed in PC tissue and was associated with larger tumor sizes, higher histologic grades, and poorer overall survival (OS). <i>B3GNT3</i> overexpression was associated with the mutation status and expression of driver genes, especially for <i>KRAS</i> and <i>SMAD4</i>. <i>B3GNT3</i> knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of PC cells. <i>B3GNT3</i> overexpression significantly correlated with decreased infiltration of tumor infiltrating lymphocytes (TILs), especially CD8⁺ T cells. Overall, our results indicate that <i>B3GTN3</i> plays a novel role in tumor progression and immunosuppression, thus serving as a potential therapeutic target in PC.