The effect of surface glycans on leukemia susceptibility to NK-mediated cytotoxicity
Yuh-Ching Twu
National Yang-Ming University, Taiwan
: J Immunol Tech Infect Dis
Abstract
The aberrant glycosylation on proteins and lipids has been implicated in malignant transformations through promoting the tumorigenesis, metastasis and the evasion from the host immunity. The I-branching β-1,6-N-acetylglucosaminyltransferase, responsible for the straight I conversion to branched I histo-blood group antigens, has been reported for its important effects on the migration, invasion and metastasis of solid tumors. First, we demonstrated that SHP-2-ERK2 signaling regulates the phosphorylation status of C/EBP by altering its binding affinity onto the IGnTC promoter region, thereby activating the synthesis of cell-surface I antigen formation during erythropoiesis. Second, we addressed how the branched I antigens on the leukemia impacted the host immuno-surveillance mediated by Natural Killer (NK) cells. The levels of I antigen presented on leukemia cells showed a positive correlation with the susceptibility to NK-mediated lysis. Third, by the conjugation assay, elevating the expression of the I antigens on the leukemia cells that can only display low level of cell surface I antigens greatly increased the sensitivity to NK cytotoxicity. Our findings suggested that branched I of the leukemia cells not only is important for NK targeting but also could serve as a potentially evaluation maker for NK-cell based leukemia treatment.
Biography
Yuh-Ching Twu is an Associate Professor at Department of Biotechnology and Laboratory Science in Medicine, National Yang-Ming University, Taiwan. She received her BS and Master degrees in Biotechnology & Laboratory Science from National Yang-Ming University and PhD degree in Biochemistry Science from National Taiwan University. She has done Post-doctoral programs in Department of Microbiology and Immunology, University of British Columbia and Terry Fox Laboratory, BC Cancer agency. She works on the molecular genetics of human blood group I locus, the regulatory mechanism of branched I formation and the correlation with immune-surveillance. yctwu@ym.edu.tw
