title: Melanoma cell lysate induces CCR7 expression and in vivo migration to draining lymph nodes of therapeutic human dendritic cells.
abstract: We have previously reported a novel method for the production of tumour-antigen-presenting cells (referred to as TAPCells) that are currently being used in cancer therapy, using an allogeneic melanoma-derived cell lysate (referred to as TRIMEL) as an antigen provider and activation factor. It was recently demonstrated that TAPCell-based immunotherapy induces T-cell-mediated immune responses resulting in improved long-term survival of stage IV melanoma patients. Clinically, dendritic cell (DC) migration from injected sites to lymph nodes is an important requirement for an effective anti-tumour immunization. This mobilization of DCs is mainly driven by the C-C chemokine receptor type 7 (CCR7), which is up-regulated on mature DCs. Using flow cytometry and immunohistochemistry, we investigated if TRIMEL was capable of inducing the expression of the CCR7 on TAPCells and enhancing their migration in vitro, as well as their in vivo relocation to lymph nodes in an ectopic xenograft animal model. Our results confirmed that TRIMEL induces a phenotypic maturation and increases the expression of surface CCR7 on melanoma patient-derived DCs, and also on the monocytic/macrophage cell line THP-1. Moreover, in vitro assays showed that TRIMEL-stimulated DCs and THP-1 cells were capable of migrating specifically in the presence of the CCR7 ligand CCL19. Finally, we demonstrated that TAPCells could migrate in vivo from the injection site into the draining lymph nodes. This work contributes to an increased understanding of the biology of DCs produced ex vivo allowing the design of new strategies for effective DC-based vaccines for treating aggressive melanomas.
authors.affiliation: Millennium Institute on Immunology and Immunotherapy, University of Chile, Santiago, Chile; Department of Conservative Dentistry, Faculty of Dentistry, University of Chile, Santiago, Chile.
authors.forename: Fermín E
authors.initials: FE
authors.lastname: González
authors.forename: Carolina
authors.initials: C
authors.lastname: Ortiz
authors.forename: Montserrat
authors.initials: M
authors.lastname: Reyes
authors.forename: Nicolás
authors.initials: N
authors.lastname: Dutzan
authors.forename: Vyomesh
authors.initials: V
authors.lastname: Patel
authors.forename: Cristián
authors.initials: C
authors.lastname: Pereda
authors.forename: Maria A
authors.initials: MA
authors.lastname: Gleisner
authors.forename: Mercedes N
authors.initials: MN
authors.lastname: López
authors.forename: J Silvio
authors.initials: JS
authors.lastname: Gutkind
authors.forename: Flavio
authors.initials: F
authors.lastname: Salazar-Onfray
mesh_terms: D000818:Animals; D002457:Cell Extracts / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D054400:Receptors, CCR7 / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: C515370:CCR7 protein, human; D002457:Cell Extracts; D054400:Receptors, CCR7
keywords: CCR7; dendritic cells; immunotherapy; melanoma; migration; tumour lysates