title: Adenoviral-transduced dendritic cells are susceptible to suppression by T regulatory cells and promote interleukin 17 production.
abstract: Dendritic cell (DC) vaccines offer a robust platform for the development of cancer vaccines, but their effectiveness is thought to be limited by T regulatory cells (Tregs). Recombinant adenoviruses (RAdV) have been used successfully to engineer tumor antigen expression in DCs, but the impact of virus transduction on susceptibility to suppression by Tregs is unknown. We investigated the functional consequences of exposure to adenovirus on interactions between human monocyte-derived DCs and Tregs. Since the development of Tregs is linked to that of pro-inflammatory Th17 cells, the role of Th17 cells and IL-17-producing Tregs in the context of DC-based immunotherapies was also investigated. We found that Tregs potently suppressed the co-stimulatory capacity of RAdV-transduced DCs, regardless of whether the DCs were maturated by inflammatory cytokines or by exposure to Th1 or Th17 cells. Furthermore, exposure of Tregs to RAdV-exposed DCs increased IL-17 production and suppressive capacity, and correlated with enhanced secretion of IL-1β and IL-6 by DCs. The findings that DCs exposed to RAdV are suppressed by Tregs, promote Treg plasticity, and enhance Treg suppression indicates that strategies to limit Tregs will be required to enhance the efficacy of such DC-based immunotherapies.
authors.affiliation: Department of Surgery, Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, 950 West 28th Ave, Vancouver, BC V5Z4H4, Canada.
authors.forename: Adele Y
authors.initials: AY
authors.lastname: Wang
authors.forename: Sarah Q
authors.initials: SQ
authors.lastname: Crome
authors.forename: Kristina M
authors.initials: KM
authors.lastname: Jenkins
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Medin
authors.forename: Jonathan L
authors.initials: JL
authors.lastname: Bramson
authors.forename: Megan K
authors.initials: MK
authors.lastname: Levings
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D019496:Cancer Vaccines; D002454:Cell Differentiation / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology* / Q000821:virology; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D008213:Lymphocyte Activation; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D015854:Up-Regulation
chemical_list: D019496:Cancer Vaccines; D016207:Cytokines; D020381:Interleukin-17; D053759:Interleukin-23