Regulation and subversion of HPV16-specific immunity in cancer patients Piersma, S.J.

Regulation and subversion of HPV16-specific immunity in cancer patients

Piersma, S.J.

Citation

Piersma, S. J. (2010, March 4). Regulation and subversion of HPV16-specific immunity in cancer patients. Retrieved from

https://hdl.handle.net/1887/15038

Version: Corrected Publisher’s Version

License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden

Downloaded from: https://hdl.handle.net/1887/15038

Note: To cite this publication please use the final published version (if applicable).

RegulationÊ andÊ subversionÊ ofÊ cancerÊ patients

Proefschrift

terÊ verkrijgingÊ van

deÊ graadÊ vanÊ DoctorÊ aanÊ deÊ UniversiteitÊ Leiden, volgensÊ besluitÊ vanÊ hetÊ CollegeÊ voorÊ Promoties

teÊ verdedigenÊ opÊ donderdagÊ 4Ê maartÊ 2010 klokkeÊ 16.15Ê uur

SytseÊ JanÊ Piersma

PROMOTORES|

CO-PROMOTOR|

OVERIGE LEDEN|

PROMOTIECOMMISSIE Prof.dr. H.W.R. Nortier Prof.dr. C.J.M. Melief

Prof.dr. G.G. Kenter (VUMC/AMC/NKI-AVL, Amsterdam)

Dr. S.H. van der Burg

Prof.dr. P. Romero (LICR, Lausanne, Zwitserland) Prof.dr. T.N. Schumacher (NKI-AVL, Amsterdam) Prof.dr. H.W.Nijman (UMCG, Groningen)

Prof.dr. T.H.M. Ottenhoff

Design and contents, 2010, Sytse J. Piersma, Leiden, the Netherlands ISBN/EAN 9789461080165

Printed by Gildeprint Drukkerijen, Enschede, the Netherlands

The studies described in this thesis were performed in the department of Clinical Oncology in collaboration with the departments of Immunohematology and Blood Transfusion, Pathology and Gynecology at the Leiden University Medical Center and the Haga Teaching Hospital and were funded by NWO ZonMw (917.56.311)

Niets uit deze uitgave mag worden verveelvoudigd en/of openbaar gemaakt worden zonder voorafgaande schriftelijke toestemming van de autheur. No part of this thesis may be reproduced in any form without written permission from the author.

Publication of this thesis was financially supported by J.E. Jurriaanse Stichting, Bontius Stichting, BD Bioscience, Greiner Bio-One and Corning BV

aan papa en mama voor Inge

Contents

1 2

3

4.1

4.2

5

6

7

General introduction | 8

High number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in

patients with large early-stage cervical cancer | 22

Human papilloma virus specific T cells infiltrating cervical cancer and draining lymph nodes show remarkably frequent use of HLA- DQ and –DP as a Restriction Element | 34

Association of cervical cancer with the presence of CD4+ regulatory T cells specific for human papillomavirus antigens |46

Induction of tumor-specific CD4+ and CD8+ T-cell immunity in cervical cancer patients by a human papillomavirus type 16 E6 and E7 long peptides vaccine | 56

Surgery followed by persistence of high-grade squamous intraepithelial lesions is associated with the induction of a dysfunctional HPV16-specific T-cell response | 68

Healthy donor derived IL-10 producing influenza virus M1-specific CD4 T-cells encompass FOXP3+ and FOXP3- T-regulatory cells as a consequence of previous acute infection | 78

Summary and general discussion | 88 Nederlandse samenvatting | 102 Curriculum vitae | 108

Dankwoord | 110