Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses.
The development of vaccines inducing efficient CD8(+) T cell responses is the focus of intense research. Dendritic cells (DCs) expressing the XCR1 chemokine receptor, also known as CD103(+) or CD8α(+) DCs, excel in the presentation of extracellular Ags to CD8(+) T cells. Because of its high numbers of DCs, including XCR1(+) DCs, the skin dermis is an attractive site for vaccine administration. By creating laser-generated micropores through the epidermis, we targeted a model protein Ag fused to XCL1, the ligand of XCR1, to dermal XCR1(+) DCs and induced Ag-specific CD8(+) and CD4(+) T cell responses. Efficient immunization required the emigration of XCR1(+) dermal DCs to draining lymph nodes and occurred irrespective of TLR signaling. Moreover, a single intradermal immunization protected mice against melanoma tumor growth in prophylactic and therapeutic settings, in the absence of exogenous adjuvant. The mild inflammatory milieu created in the dermis by skin laser microporation itself most likely favored the development of potent T cell responses in the absence of exogenous adjuvants. The existence of functionally equivalent XCR1(+) dermal DCs in humans should permit the translation of laser-assisted intradermal delivery of a tumor-specific vaccine targeting XCR1(+) DCs to human cancer immunotherapy. Moreover, considering that the use of adjuvants in vaccines is often associated with safety issues, the possibility of inducing protective responses against melanoma tumor growth independently of the administration of exogenous adjuvants should facilitate the development of safer vaccines.
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; Department of Dermatology, Charité University Medicine, 10117 Berlin, Germany;
Dorothea
D
Terhorst
K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo 0424, Norway;
Even
E
Fossum
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France;
Anna
A
Baranska
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France;
Samira
S
Tamoutounour
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France;
Camille
C
Malosse
Department of Molecular Allergology, Swiss Institute of Allergy and Asthma Research, University of Zürich, Davos 7270, Switzerland;
Mattia
M
Garbani
Pantec Biosolutions, 9491 Ruggell, Liechtenstein; and.
Reinhard
R
Braun
Pantec Biosolutions, 9491 Ruggell, Liechtenstein; and.
Elmira
E
Lechat
Department of Molecular Allergology, Swiss Institute of Allergy and Asthma Research, University of Zürich, Davos 7270, Switzerland;
Reto
R
Crameri
K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo 0424, Norway; Center for Immune Regulation, Institute of Immunology, University of Oslo and Oslo University Hospital Rikshospitalet, Oslo 0424 Norway.
Bjarne
B
Bogen
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr.
Sandrine
S
Henri
Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Université, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr.
Bernard
B
Malissen
D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism; D000818:Animals; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000276:immunology*; D019744:Chemokines, C / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004195:Disease Models, Animal; D007271:Injections, Intradermal; D008546:Melanoma, Experimental; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D009369:Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D010047:Ovalbumin / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D019707:Receptors, Chemokine / Q000235:genetics / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology; D047368:Tumor Burden / Q000276:immunology
D033942:Adaptor Proteins, Vesicular Transport; D019496:Cancer Vaccines; D019744:Chemokines, C; D053594:Myeloid Differentiation Factor 88; D010047:Ovalbumin; D019707:Receptors, Chemokine; C476286:Ticam1 protein, mouse; C551408:XC chemokine receptor 1, mouse; C486249:Xcl1 protein, mouse