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

Beta-1,3-N-acetylglucosaminyltransferase 3 (B3GNT3) 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 B3GNT3 in immunosuppression in pancreatic cancer (PC). This study on B3GNT3 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 B3GNT3 were investigated through bioinformatic analysis and in vitro studies. Potential associations between the expression of B3GNT3 and tumor immunity were mainly analyzed by single-sample gene set enrichment analysis (ssGSEA) and immunofluorescence in tissue microarray (TMA). B3GNT3 overexpression was observed in PC tissue and was associated with larger tumor sizes, higher histologic grades, and poorer overall survival (OS). B3GNT3 overexpression was associated with the mutation status and expression of driver genes, especially for KRAS and SMAD4. B3GNT3 knockdown inhibited the proliferation, invasion, and epithelial-mesenchymal transition (EMT) of PC cells. B3GNT3 overexpression significantly correlated with decreased infiltration of tumor infiltrating lymphocytes (TILs), especially CD8+ T cells. Overall, our results indicate that B3GTN3 plays a novel role in tumor progression and immunosuppression, thus serving as a potential therapeutic target in PC.