Fucoidin enhances dendritic cell-mediated T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells.
Scavenger receptor A (SR-A) plays a crucial role in affecting the dendritic cell-mediated presentation of cancer testis antigens to T cells against human cancer cells. Here we use a dendritic cell-mediated model to verify that a sulphated polysaccharide, fucoidin, can regulate the adverse regulatory function of SR-A, and lead to the up-regulation of the anti-tumor immunological response. SR-A is a receptor of calreticulin (CRT) existing on the surface of dendritic cells (DCs). CRT is a specific receptor for a NY-ESO-1 cancer testis antigen, and CRT itself is responsible for the cross-presentation of NY-ESO-1 to CD8+ cells and the induction of anti-tumor immunity. Flow cytometrical analysis (FACS) showed that fucoidin was able to significantly enhance the binding ratio of NY-ESO-1 to human DCs in a concentration dependent manner, and that the addition of fucoidin promoted the DC maturation upon stimulation of NY-ESO-1. Results from a cytotoxicity assay indicated that fucoidin-treated DCs stimulated the CD8+ T cells more effectively than non-treated DCs via a cross-presentation pathway. Furthermore, it was found that after stimulated by fucoidin-treated DCs, the CD8+ T cells can release more IFN-gamma than non-fucoidin-treated cells as detected by intracellular IFN-gamma staining. We conclude that fucoidin enhances the cross-presentation of NY-ESO-1 to T cells leading to an increase of T-cell cytotoxicity against NY-ESO-1 expressing human cancer cells.
Hu
Yaling
Y
Department of Biology, The Hong Kong University of Science and Technology, Kowloon, Hong Kong SAR, China.
Cheng
Samuel Chak-Sum
SC
Chan
Kin-Tak
KT
Ke
Yan
Y
Xue
Bofu
B
Sin
Fion Wan-Yee
FW
Zeng
Chenjie
C
Xie
Yong
Y
D000951:Antigens, Neoplasm / Q000276:immunology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D045142:Cross-Priming / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology*; D009369:Neoplasms / Q000276:immunology* / Q000378:metabolism; D011134:Polysaccharides / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; C104948:CTAG1B protein, human; D008565:Membrane Proteins; D011134:Polysaccharides; C007789:fucoidan