title: Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.
abstract: Human papillomaviruses (HPV) establish persistent infections because of evolved immune evasion mechanisms, particularly HPV-mediated suppression of the immune functions of Langerhans cells (LC), the antigen presenting cells of the epithelium. Polyinosinic-polycytidilic acid (Poly-I:C) is broadly immunostimulatory with the ability to enhance APC expression of costimulatory molecules and inflammatory cytokines resulting in T cell activation. Here we investigated the activation of primary human LC derived from peripheral blood monocytes after exposure to HPV16 virus like particles followed by treatment with stabilized Poly-I:C compounds (s-Poly-I:C), and their subsequent induction of HPV16-specific T cells. Our results indicate that HPV16 particles alone were incapable of inducing LC activation as demonstrated by the lack of costimulatory molecules, inflammatory cytokines, chemokine-directed migration, and HPV16-specific CD8+T cellsin vitro. Conversely, s-Poly-I:C caused significant upregulation of costimulatory molecules and induction of chemokine-directed migration of LC that were pre-exposed to HPV16. In HLA-A*0201-positive donors, s-Poly-I:C treatment was able to induce CD8+T cell immune responses against HPV16-derived peptides. Thus, s-Poly-I:C compounds are attractive for translation into therapeutics in which they could potentially mediate clearance of persistent HPV infection.
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.|Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, California, USA.
authors.forename: Diane M
authors.initials: DM
authors.lastname: Da Silva
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Woodham
authors.affiliation: Groningen International Program of Science in Medicine, University of Groningen, Groningen, The Netherlands.
authors.forename: Laurie K
authors.initials: LK
authors.lastname: Rijkee
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Skeate
authors.affiliation: Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, USA.
authors.forename: Julia R
authors.initials: JR
authors.lastname: Taylor
authors.affiliation: Groningen International Program of Science in Medicine, University of Groningen, Groningen, The Netherlands.
authors.forename: Maaike E
authors.initials: ME
authors.lastname: Koopman
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
authors.forename: Heike E
authors.initials: HE
authors.lastname: Brand
authors.affiliation: Department of Medicine, University of Southern California, Los Angeles, California, USA.
authors.forename: Michael K
authors.initials: MK
authors.lastname: Wong
authors.affiliation: Akela Pharma Inc., Austin, Texas, USA.
authors.forename: Greg M
authors.initials: GM
authors.lastname: McKee
authors.affiliation: Oncovir, Inc., Washington, D.C., USA.
authors.forename: Andres M
authors.initials: AM
authors.lastname: Salazar
authors.affiliation: Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.|Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, California, USA.|Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, USA.
authors.forename: W Martin
authors.initials: WM
authors.lastname: Kast
keywords: HPV16; Langerhans cells; immune escape; papillomavirus