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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.

Author information

1
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
2
Department of Obstetrics & Gynecology, University of Southern California, Los Angeles, California, USA.
3
Department of Molecular Microbiology & Immunology, University of Southern California, Los Angeles, California, USA.
4
Groningen International Program of Science in Medicine, University of Groningen, Groningen, The Netherlands.
5
Department of Medicine, University of Southern California, Los Angeles, California, USA.
6
Akela Pharma Inc., Austin, Texas, USA.
7
Oncovir, Inc., Washington, D.C., USA.
#
Contributed equally

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 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.

KEYWORDS:

HPV16; Langerhans cells; immune escape; papillomavirus

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