Melanoma-infiltrating dendritic cells induce protective antitumor responses mediated by T cells.
Dendritic cells are the most potent antigen-presenting cells inducing innate and adaptive immune response. Dendritic cells infiltrate melanomas, but their ability to induce host antitumor immunity remains obscure. In a previous study, we have observed that melanoma-infiltrating dendritic cells have the capacity to process antigens and migrate to lymph nodes to prime T lymphocytes. Here, we observed that melanoma-infiltrating dendritic cells extracted from melanoma without any additional manipulations were able to protect naive mice against a lethal challenge with the tumor. Remarkably, this was achieved with reinjection of 10(5) melanoma-infiltrating dendritic cells, a number that did not exceed the total number of melanoma-infiltrating dendritic cells recovered from one single tumor. Three observations indicate that protection was due to the natural loading of melanoma-infiltrating dendritic cells with tumor antigens. First, the protective effect was not observed with equivalent numbers of bone marrow-derived dendritic cells. Second, the protection induced was specific for the tumor from which the tumor-infiltrating dendritic cells were isolated. Third, depletion experiments indicate that both CD4+ and CD8+ T lymphocytes were required during the effector phase of the antitumor response. Hence, designing strategies aimed at rendering melanoma-infiltrating dendritic cells visible to host T cells may boost spontaneous antitumor immunity.
Preynat-Seauve
Olivier
O
Louis Jeantet Skin Cancer Laboratory, Department of Dermatology, Geneva University Hospital, Geneva, Switzerland. Olivier.Preynat-Seauve@medecine.unige.ch
Contassot
Emmanuel
E
Schuler
Prisca
P
French
Lars E
LE
Huard
Bertrand
B
D019264:Adoptive Transfer; D000818:Animals; D000951:Antigens, Neoplasm / Q000276:immunology*; D016026:Bone Marrow Transplantation; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation*; D008213:Lymphocyte Activation; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000601:surgery / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010446:Peptide Fragments / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013997:Time Factors
D000951:Antigens, Neoplasm; C110366:OVA-8; D010446:Peptide Fragments; D011948:Receptors, Antigen, T-Cell; D010047:Ovalbumin