THESIS
2008
xiii, 69 leaves : ill. (some col.) ; 30 cm
Abstract
Scavenger receptor A (SR-A) has been found able to negatively regulate antitumor immunity, and Fucoidin is a promising inhibitor of SR-A. Calreticulin (CRT) on dendritic cells (DC) surface is a receptor for a cancer-testis antigen (CTA), NY-ESO-1, and CRT is responsible for the cross-presentation of NY-ESO-1 to T cells and the induction of antitumor immunity, and it may interact with SR-A for the uptake of exogenous peptides. Here we tried to verify whether the inhibition of SR-A with fucoidin, could induce an up-regulation of the antitumor immunity....[
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Scavenger receptor A (SR-A) has been found able to negatively regulate antitumor immunity, and Fucoidin is a promising inhibitor of SR-A. Calreticulin (CRT) on dendritic cells (DC) surface is a receptor for a cancer-testis antigen (CTA), NY-ESO-1, and CRT is responsible for the cross-presentation of NY-ESO-1 to T cells and the induction of antitumor immunity, and it may interact with SR-A for the uptake of exogenous peptides. Here we tried to verify whether the inhibition of SR-A with fucoidin, could induce an up-regulation of the antitumor immunity.
In my study, flow cytometrical (FACS) analysis of NY-ESO-1 binding assay showed that the application of fucoidin significantly increases the binding ratio of NY-ESO-1 to human DCs in a concentration dependent manner. FACS analysis of DC maturation markers demonstrated that fucoidin promoted DCs maturation on stimulation of NY-ESO-1. Furthermore, the cytotoxicity assay of CD8+ T cells indicated that fucoidin-treated DCs stimulate CTL more effectively than non-treated DCs through a cross-presentation pathway. Meanwhile, through intracellular IFN-γ staining, it is found that CD8+ T cells stimulated by fucoidin treated DCs release more IFN-γ than non-fucoidin treated cells. It can be concluded that fucoidin enhances the cross-presentation of NY-ESO-1 to T-cells leading to an increase of the T cell cytotoxicity against NY-ESO-1 expressing human cancer cells, and fucoidin can significantly up-regulate the antitumor immunity.
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