title: Tumor-infiltrating dendritic cells are potent antigen-presenting cells able to activate T cells and mediate tumor rejection.
abstract: Dendritic cells (DC) are potent inducers of immune responses. DC have been shown to infiltrate tumors, but very little is known about the functional status of these naturally occurring tumor-infiltrating DC (TIDC). In this study, the status and function of TIDC from several types of mouse melanoma were investigated in detail. CD11c+/MHC II+ cells, consistent with a DC phenotype, were found in all of transplantable or spontaneous melanomas studied. These TIDC were predominantly myeloid (CD11c+/CD8alpha-/B220-) in nature with small numbers of plasmacytoid (CD11c+/B220+). TIDC had an intermediate maturation phenotype with some expression of costimulatory molecules and the capacity to take up particles. Upon culture overnight ex vivo, the TIDC markedly up-regulated the expression of costimulatory molecules and also increased IL-12 production. Importantly, such ex vivo-matured TIDC pulsed with OVA were able to migrate to lymph nodes, to activate naive OVA-specific CD4+ and CD8+ T cells, and to confer protection against a challenge with OVA-expressing tumor cells. In conclusion, melanomas are infiltrated by functional DC that can act as fully competent APC. These APC have the potential to be manipulated and may therefore represent a promising target for cancer immunotherapy.
authors.affiliation: Louis Jeantet Skin Cancer Laboratory, Department of Pathology and Immunology, Geneva University Medical Center, Geneva, Switzerland. oliver.preynat-seauve@medecine.unige.ch
authors.forename: Olivier
authors.initials: O
authors.lastname: Preynat-Seauve
authors.forename: Prisca
authors.initials: P
authors.lastname: Schuler
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Contassot
authors.forename: Friedrich
authors.initials: F
authors.lastname: Beermann
authors.forename: Bertrand
authors.initials: B
authors.lastname: Huard
authors.forename: Lars E
authors.initials: LE
authors.lastname: French
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D016130:Immunophenotyping; D008213:Lymphocyte Activation / Q000276:immunology; D008545:Melanoma / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology*