dendritic cells crosspresent antigens from live b16 cells more efficiently than from apoptotic cells and protect from melanoma in a therapeutic model从生活b16转椅细胞树突细胞crosspresent抗原更有效地比从凋亡细胞和保护黑色素瘤的治疗模式.pdfVIP

Dendritic Cells Crosspresent Antigens from Live B16 Cells More Efficiently than from Apoptotic Cells and Protect from Melanoma in a Therapeutic Model Diana Matheoud1,2,3.¤, Camille Baey1,2,3., Lene Vimeux1,2,3, Andy Tempez1,2,3, Michael Valente1,2,3, 1,2,3 ` 1,2,3 1,2,3 1,2,3 Pauline Louche , Agnes Le Bon , Anne Hosmalin * , Vincent Feuillet * ´ 1 Inserm, U1016, Institut Cochin, Paris, France, 2 Cnrs, UMR8104, Paris, France, 3 Universite Paris Descartes, Paris, France Abstract Dendritic cells (DC) are able to elicit anti-tumoral CD8+ T cell responses by cross-presenting exogenous antigens in association with major histocompatibility complex (MHC) class I molecules. Therefore they are crucial actors in cell-based cancer immunotherapy. Although apoptotic cells are usually considered to be the best source of antigens, live cells are also able to provide antigens for cross-presentation by DC. We have recently shown that prophylactic immunotherapy by DC after capture of antigens from live B16 melanoma cells induced strong CD8+ T-cell responses and protection against a lethal tumor challenge in vivo in C57Bl/6 mice. Here, we showed that DC cross-presenting antigens from live B16 cells can also inhibit melanoma lung dissemination in a therapeutic protocol in mice. DC were first incubated with live tumor cells for antigen uptake and processing, then purified and irradiated for safety prior to injection. This treatment induced stronger tumor-specific CD8+ T-cell responses than treatment by DC cross-presenting antigens from apoptotic cells. Apoptotic B16 cells induced more IL-10 secretion by DC