PMID- 25941327 OWN - NLM STAT- MEDLINE DCOM- 20150820 LR - 20150606 IS - 1550-6606 (Electronic) IS - 0022-1767 (Linking) VI - 194 IP - 12 DP - 2015 Jun 15 TI - Laser-assisted intradermal delivery of adjuvant-free vaccines targeting XCR1+ dendritic cells induces potent antitumoral responses. PG - 5895-902 LID - 10.4049/jimmunol.1500564 [doi] AB - 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 CD8alpha(+) 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. CI - Copyright (c) 2015 by The American Association of Immunologists, Inc. FAU - Terhorst, Dorothea AU - Terhorst D AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; Department of Dermatology, Charite University Medicine, 10117 Berlin, Germany; FAU - Fossum, Even AU - Fossum E AD - K.G. Jebsen Centre for Influenza Vaccine Research, University of Oslo, Oslo 0424, Norway; FAU - Baranska, Anna AU - Baranska A AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; FAU - Tamoutounour, Samira AU - Tamoutounour S AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; FAU - Malosse, Camille AU - Malosse C AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; FAU - Garbani, Mattia AU - Garbani M AD - Department of Molecular Allergology, Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos 7270, Switzerland; FAU - Braun, Reinhard AU - Braun R AD - Pantec Biosolutions, 9491 Ruggell, Liechtenstein; and. FAU - Lechat, Elmira AU - Lechat E AD - Pantec Biosolutions, 9491 Ruggell, Liechtenstein; and. FAU - Crameri, Reto AU - Crameri R AD - Department of Molecular Allergology, Swiss Institute of Allergy and Asthma Research, University of Zurich, Davos 7270, Switzerland; FAU - Bogen, Bjarne AU - Bogen B AD - 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. FAU - Henri, Sandrine AU - Henri S AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr. FAU - Malissen, Bernard AU - Malissen B AD - Centre d'Immunologie de Marseille-Luminy, UM2 Aix-Marseille Universite, 13288 Marseille Cedex 9, France; INSERM U1104, 13288 Marseille Cedex 9, France; Centre National de la Recherche Scientifique, Unite Mixte de Recherche 7280, 13288 Marseille Cedex 9, France; bernardm@ciml.univ-mrs.fr henri@ciml.univ-mrs.fr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20150504 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (Adaptor Proteins, Vesicular Transport) RN - 0 (Cancer Vaccines) RN - 0 (Chemokines, C) RN - 0 (Myeloid Differentiation Factor 88) RN - 0 (Receptors, Chemokine) RN - 0 (TICAM-1 protein, mouse) RN - 0 (XC chemokine receptor 1, mouse) RN - 0 (Xcl1 protein, mouse) RN - 9006-59-1 (Ovalbumin) SB - IM MH - Adaptor Proteins, Vesicular Transport/metabolism MH - Animals MH - Cancer Vaccines/administration & dosage/*immunology MH - Chemokines, C/genetics/metabolism MH - Dendritic Cells/*immunology/*metabolism MH - Disease Models, Animal MH - Injections, Intradermal MH - Melanoma, Experimental MH - Mice MH - Mice, Knockout MH - Myeloid Differentiation Factor 88/metabolism MH - Neoplasms/*immunology/pathology/therapy MH - Ovalbumin/genetics/immunology MH - Protein Binding MH - Receptors, Chemokine/genetics/*metabolism MH - T-Lymphocyte Subsets/immunology MH - Tumor Burden/immunology EDAT- 2015/05/06 06:00 MHDA- 2015/08/21 06:00 CRDT- 2015/05/06 06:00 PHST- 2015/03/10 00:00 [received] PHST- 2015/04/15 00:00 [accepted] PHST- 2015/05/06 06:00 [entrez] PHST- 2015/05/06 06:00 [pubmed] PHST- 2015/08/21 06:00 [medline] AID - jimmunol.1500564 [pii] AID - 10.4049/jimmunol.1500564 [doi] PST - ppublish SO - J Immunol. 2015 Jun 15;194(12):5895-902. doi: 10.4049/jimmunol.1500564. Epub 2015 May 4.