Rijkee, L.K. (Laurie) (2014) Human Papillomavirus type 16 suppression of Langerhans cell maturation is reversed by a stabilized form of PolyIC. thesis, Medicine.
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Abstract
Human papillomavirus type 16 (HPV16) is the major cancer-causing strain of high-risk HPV and is implicated in causing more than 50% of all cervical cancers, which is the second most lethal form of cancer in women worldwide. Langerhans cells (LC) are the first line of defense the immune system has if encountering HPV16 within the epithelium and are therefore responsible for the initiation of an effective immune response against the virus. However, activation of LC in the form of phenotypic and functional changes does not occur with HPV16 infection due to the immunosuppressive effects HPV16 has on LC. The specific aim of this project was to determine whether a stabilized form of the toll-like receptor 3 (TLR3) agonist polyinosinic-polycytidylic acid (s-PolyIC) is able to reverse the suppression of LC immune function caused by HPV16. This study shows that s-PolyIC is able to activate LC derived from healthy donors and from patients with cervical intraepithelial neoplasia (CIN) after being exposed to HPV16 pseudovirions (PsV). LC from healthy and CIN donors treated with s-PolyIC after HPV16 exposure displayed a 1.5-fold increase in expression of the activation-associated surface marker MHCII, a 6-fold increase in CD86, and a down-regulation of CD1a compared to untreated or HPV16 only treated LC indicating phenotypical LC maturation with s-PolyIC. Additionally, an increase in the migratory ability of LC exposed to HPV16 PsV was observed after treatment with s-PolyIC from both healthy and CIN donors compared to untreated and HPV16 only treated LC, as well as an increase in the secretion of pro-inflammatory cytokines and chemokines such as IL-8 and TNFα. From these data we conclude that s-PolyIC is able to induce phenotypical and functional maturation of LC exposed to HPV16 from both healthy and CIN donors.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Kallenberg, prof.dr. C.G.M. |
| Supervisor name: | Kast, W. Martin PhD and Woodham, A.W. PhD candidate and Norris Comprehensive Cancer Center, University of Southern C |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:04 |
| Last Modified: | 25 Jun 2020 11:04 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2425 |
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