Revised Abstract: Tumors particularly, particularly clinical and experimental melanomas, express peptides that can be presented on MHC class I products to cytolytic T lymphocytes [CTLs]. The example to be studied here is the mouse B16 melanoma, for which gp175 and TRP-2 peptides have been defined. Yet these peptide-specific T cells are not expanded in tumor bearing mice. We hypothesize that tumors are not presented by the dendritic cell [DC] system that normally initiates immunity, and therefore, that targeting of melanoma to DCs should elicit tumor immunity and resistance. Under the appropriate developmental conditions, DCs efficiently form MHC-peptide complexes, express high levels of T cell co-stimulatory molecules, and migrate to lymphoid tissues to initiate immunity. Previously, potent and specialized antigen presenting DCs have not been available in sufficient numbers, nor has it been evident how to load DCs with cellular antigens. These obstacles are being overcome. Now it is possible to generate large numbers of cells from mouse marrow precursors, and these process peptides from other apoptotic and necrotic cells. Therefore our aims are to 1] charge DCs with dying B16 melanoma ex vivo and use these to optimize the induction of tumor immunity in vivo; 2] target dying B16 melanoma cells to DCs in situ to induce immunity; 3] evaluate if DCs can process a helper epitope within B16 tumors that are growing in situ; and 4] analyze subsets of DCs for their capacity to elicit melanoma immunity.
| Speake, Cate; Presnell, Scott; Domico, Kelly et al. (2015) An interactive web application for the dissemination of human systems immunology data. J Transl Med 13:196 |
| Rongvaux, Anthony; Willinger, Tim; Martinek, Jan et al. (2014) Development and function of human innate immune cells in a humanized mouse model. Nat Biotechnol 32:364-72 |
| Palucka, Karolina; Banchereau, Jacques (2013) Human dendritic cell subsets in vaccination. Curr Opin Immunol 25:396-402 |
| Palucka, Karolina; Banchereau, Jacques (2013) Dendritic-cell-based therapeutic cancer vaccines. Immunity 39:38-48 |
| Obermoser, Gerlinde; Presnell, Scott; Domico, Kelly et al. (2013) Systems scale interactive exploration reveals quantitative and qualitative differences in response to influenza and pneumococcal vaccines. Immunity 38:831-44 |
| Banchereau, Jacques; Thompson-Snipes, LuAnn; Zurawski, Sandra et al. (2012) The differential production of cytokines by human Langerhans cells and dermal CD14(+) DCs controls CTL priming. Blood 119:5742-9 |
| Banchereau, Jacques; Zurawski, Sandra; Thompson-Snipes, LuAnn et al. (2012) Immunoglobulin-like transcript receptors on human dermal CD14+ dendritic cells act as a CD8-antagonist to control cytotoxic T cell priming. Proc Natl Acad Sci U S A 109:18885-90 |
| Palucka, Karolina; Banchereau, Jacques (2012) Cancer immunotherapy via dendritic cells. Nat Rev Cancer 12:265-77 |
| Bentebibel, Salah-Eddine; Schmitt, Nathalie; Banchereau, Jacques et al. (2011) Human tonsil B-cell lymphoma 6 (BCL6)-expressing CD4+ T-cell subset specialized for B-cell help outside germinal centers. Proc Natl Acad Sci U S A 108:E488-97 |
| Ueno, Hideki; Klechevsky, Eynav; Schmitt, Nathalie et al. (2011) Targeting human dendritic cell subsets for improved vaccines. Semin Immunol 23:21-7 |
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