Dendritic Cells Charged with Apoptotic Tumor Cells Induce Long-Lived Protective CD4+ and CD8+ T Cell Immunity against B16 Melanoma

• Autores: Goldszmid, R.S.; Idoyaga, J.; Bravo, A.I.; Steinman, R.; Mordoh, J.; Wainstok, R.
• Año de publicación: 2003
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: J. Immunol. 2003;171(11):5940-5947
• Materia: CD4 antigen; CD8 antigen; gamma interferon; major histocompatibility antigen class 1; tyrosinase related protein 2; animal cell; animal experiment; animal model; antigen expression; antigen recognition; apoptosis; article; bone marrow cell; cell culture; cell maturation; cell migration; cell stimulation; cellular immunity; coculture; controlled study; cytokine release; cytolysis; dendritic cell; experiment; immunogenicity; in vitro study; in vivo study; injection; inoculation; lymph node; lymphatic drainage; lymphocyte depletion; male; melanoma cell; mouse; nonhuman; priority journal; protein expression; provocation test; T lymphocyte; target cell; tumor cell; tumor immunity; vaccination
• Institución: Universidad Nacional de Buenos Aires. Facultad de Ciencias Exactas y Naturales

Dendritic cells (DCs) are potent APCs and attractive vectors for cancer immunotherapy. Using the B16 melanoma, a poorly immunogenic experimental tumor that expresses low levels of MHC class I products, we investigated whether DCs loaded ex vivo with apoptotic tumor cells could elicit combined CD4+ and CD8+ T cell dependent, long term immunity following injection into mice. The bone marrow-derived DCs underwent maturation during overnight coculture with apoptotic melanoma cells. Following injection, DCs migrated to the draining lymph nodes comparably to control DCs at a level corresponding to ∼0.5% of the injected inoculum. Mice vaccinated with tumor-loaded DCs were protected against an intracutaneous challenge with B16, with 80% of the mice remaining tumor-free 12 wk after challenge. CD4+ and CD8+ T cells were efficiently primed in vaccinated animals, as evidenced by IFN-γ secretion after in vitro stimulation with DCs loaded with apoptotic B16 or DCs pulsed with the naturally expressed melanoma Ag, tyrosinase-related protein 2. In addition, B16 melanoma cells were recognized by immune CD8 + T cells in vitro, and cytolytic activity against tyrosinase-related protein 2180-188-pulsed target cells was observed in vivo. When either CD4+ or CD8+ T cells were depleted at the time of challenge, the protection was completely abrogated. Mice receiving a tumor challenge 10 wk after vaccination were also protected, consistent with the induction of tumor-specific memory. Therefore, DCs loaded with cells undergoing apoptotic death can prime melanoma-specific helper and CTLs and provide long term protection against a poorly immunogenic tumor in mice.
Fil:Goldszmid, R.S. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.
Fil:Idoyaga, J. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina.