Objective:Pancreatic ductal adenocarcinoma(PDAC)is one of the most challenging malignancies in the digestive system.Immune evasion is a crucial factor leading to poor prognosis in patients.This study aims to investiga...Objective:Pancreatic ductal adenocarcinoma(PDAC)is one of the most challenging malignancies in the digestive system.Immune evasion is a crucial factor leading to poor prognosis in patients.This study aims to investigate the molecular mechanisms of immune evasion in PDAC cells.Methods:We used The Cancer Genome Atlas(TCGA),and Genotype-Tissue Expression Project(GTEx),Gene Expression Omnibus(GEO)databases,and immunohistochemistry to analyze the expression patterns of Beta-1,3-N-acetylglucosaminyltransferase 3(B3GNT3)in normal pancreatic tissues and tumor tissues.We explored the biological pathways involving B3GNT3 through RNA-sequencing(RNA-seq)and gene ontology(GO)enrichment analysis.The correlation between B3GNT3 and major histocompatibility complex class I(MHC-I)levels was examined using flow cytometry.In addition,by establishing a mouse PDAC orthotopic model,we investigated the relationship between B3GNT3,PDAC progression,and CD8+T cell function.Results:B3GNT3 mRNA levels are significantly higher in tumor samples compared with normal tissue,and its expression is negatively correlated with patient prognosis.RNA-seq analysis suggests B3GNT3 may impact MHC-I mediated antigen presentation.Knockdown of B3GNT3 increases MHC-I levels on tumor cells,while overexpression decreases them.In a mouse PDAC model,B3GNT3 knockdown inhibits tumor growth and increases CD8+T cell infiltration.Conclusions:The expression level of B3GNT3 in PDAC cells is negatively correlated with MHC-I levels,thereby affecting the ability of CD8+T cells to recognize tumor cells and exert their cytotoxic function,making tumor cells more prone to immune evasion.展开更多
基金supported by the Scientific Research Foundation of SUMHS(No.SSF-23-15-002 to XX).
文摘Objective:Pancreatic ductal adenocarcinoma(PDAC)is one of the most challenging malignancies in the digestive system.Immune evasion is a crucial factor leading to poor prognosis in patients.This study aims to investigate the molecular mechanisms of immune evasion in PDAC cells.Methods:We used The Cancer Genome Atlas(TCGA),and Genotype-Tissue Expression Project(GTEx),Gene Expression Omnibus(GEO)databases,and immunohistochemistry to analyze the expression patterns of Beta-1,3-N-acetylglucosaminyltransferase 3(B3GNT3)in normal pancreatic tissues and tumor tissues.We explored the biological pathways involving B3GNT3 through RNA-sequencing(RNA-seq)and gene ontology(GO)enrichment analysis.The correlation between B3GNT3 and major histocompatibility complex class I(MHC-I)levels was examined using flow cytometry.In addition,by establishing a mouse PDAC orthotopic model,we investigated the relationship between B3GNT3,PDAC progression,and CD8+T cell function.Results:B3GNT3 mRNA levels are significantly higher in tumor samples compared with normal tissue,and its expression is negatively correlated with patient prognosis.RNA-seq analysis suggests B3GNT3 may impact MHC-I mediated antigen presentation.Knockdown of B3GNT3 increases MHC-I levels on tumor cells,while overexpression decreases them.In a mouse PDAC model,B3GNT3 knockdown inhibits tumor growth and increases CD8+T cell infiltration.Conclusions:The expression level of B3GNT3 in PDAC cells is negatively correlated with MHC-I levels,thereby affecting the ability of CD8+T cells to recognize tumor cells and exert their cytotoxic function,making tumor cells more prone to immune evasion.
