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Papillomavirus Res. 2015 Dec 1;1:12-21. doi: 10.1016/j.pvr.2015.05.001.

Human papillomavirus-exposed Langerhans cells are activated by stabilized Poly-I:C.

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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.
Groningen International Program of Science in Medicine, University of Groningen, Groningen, The Netherlands.
Department of Medicine, University of Southern California, Los Angeles, California, USA.
Akela Pharma Inc., Austin, Texas, USA.
Oncovir, Inc., Washington, D.C., USA.
Contributed equally


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 cells in 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.


HPV16; Langerhans cells; immune escape; papillomavirus

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