A Novel Tumor-Associated Pancreatic Glycoprotein Is Internalized by Human Dendritic Cells and Induces Their Maturation

摘要: Aberrant glycosylation or overexpression of cell-surface glycosylated tumor-associated Ags (TAA) distinguish neoplastic from normal cells. Interactions TAA MUC1 and HER2/neu with dendritic cells (DC) preclude efficient processing, which impairs immune responses. It is thus important to define the mechanisms interactions between DC their trafficking processing for further T cell activation. In this work, we study oncofetal fucose-rich glycovariants bile salt-dependent lipase (BSDL), expressed in pancreatic cancer tissues referred as pathological BSDL carrying fucosylated J28 glycotope (pBSDL-J28) because it characterized by mAb J28. The expression pBSDL-J28 was assessed immunohistochemistry quantified confocal microscopy. Nontumoral do not express pBSDL-J28. Using multidisciplinary approaches functional studies, provide first evidence, our knowledge, that tumoral glycoprotein rapidly internalized human through macropinocytosis endocytosis via mannose receptors then transported late endosomes processing. Interestingly, per se induced maturation increased costimulatory CD83 molecules associated cytokine secretion (IL-8 IL-6). Surprisingly, retained full ability internalize Ags, making atypical. Finally, allogeneic pBSDL-J28-treated stimulated lymphocyte proliferation. Besides, pulsing C-terminal glycopolypeptide CD40L triggered CD4(+) CD8(+) Therefore, pBSDL-J28, on tissue, may lead adequate Ag result