Regulation and subversion of HPV16-specific immunity in cancer patients

Author(s):
Piersma, S.J.
Published
2010
Publication type
Doctoral Thesis

Abstract

Cervical cancer is induced by HPV in virtually all cases, but it is still unknown how these virus-positive tumors arise in the face of immunity. In this thesis we examined the role of different arms of the adaptive immune response on cervical cancer. In previous studies, it was shown that cancer patients do have a detectable immune response against the HPV16 E6 and E7 antigens. However, in general this response was not associated with cytokine production. In the present study, the mechanism underlying this dysfunctional immune response was investigated by studying the presence, specificity and function of the local T-cell response in patients with HPV-induced cervical malignancies at different stages of disease. Low CD8/Treg ratio is a significant independent unfavorable prognostic factor in cervical cancer patients. Frequently, the tumor is also infiltrated with HPV-specific CD4+ and CD8+ T-cells which can potentially attack the tumor. The infiltrating T-cells also include HPV-specific regulatory T-cells which are able to suppress the reactivity of neighboring T-cells. Their presence may explain the failure of the immune system to control HPV-induced tumors.

Cervical cancerHuman papillomavirusImmunityT-cell responseT-regulatory cellCervical Intraepithelial Neoplasiatumor infiltrating lymphocytespeptide vaccination
Defense date
2010-03-04
Language
English
Supervisor(s)
Nortier, H.W.R.; Melief, C.J.M.; Kenter, G.G.
Advisor(s)
Burg, S.H. van der
Qualification
Ph.D.
Degree granting institution
Leiden University Medical Center (LUMC), Leiden University, Leiden
hdl
1887/15038
ISBN(s)
9789461080165

Funding

Sponsorship
funded by NWO ZonMw (917.56.311) supported by J.E. Jurriaanse Stichting, Bontius Stichting, BD Bioscience, Greiner Bio-One and Corning BV and ISA pharmaceuticals.