Document Type
Article
Publication Date
2007
Keywords
cancer vaccines, CD8-positive T-Lymphocytes, dendritic cell, melanoma B16, cellular immunity
Abstract
We report a mechanism to induce combined and long-lived CD4+ and CD8+ T cell immunity to several mouse tumors. Surprisingly, the initial source of antigen is a single low dose of tumor cells loaded with α-galactosylceramide (α-GalCer) glycolipid (tumor/Gal) but lacking co-stimulatory molecules. After tumor/Gal injection intravenously (i.v.), innate NKT and NK cells reject the tumor cells, some of which are taken up by dendritic cells (DCs). The DCs in turn cross-present glycolipid on CD1d molecules to NKT cells and undergo maturation. For B16 melanoma cells loaded with α-GalCer (B16/Gal), interferon γ-producing CD8+ T cells develop toward several melanoma peptides, again after a single low i.v. dose of B16/Gal. In all four poorly immunogenic tumors tested, a single dose of tumor/Gal i.v. allows mice to become resistant to tumors given subcutaneously. Resistance requires CD4+ and CD8+ cells, as well as DCs, and persists for 6-12 mo. Therefore, several immunogenic features of DCs are engaged by the CD1d-mediated cross-presentation of glycolipid-loaded tumor cells, leading to particularly strong and long-lived adaptive immunity.
Recommended Citation
himizu, K., Y. Kurosawa, M. Taniguchi, R. M. Steinman, and S. -I Fujii. 2007. "Cross-Presentation of Glycolipid from Tumor Cells Loaded with α-Galactosylceramide Leads to Potent and Long-Lived T Cell-Mediated Immunity Via Dendritic Cells." Journal of Experimental Medicine 204 (11): 2641-2653
Comments
Open Access