Cover Page
The handle http://hdl.handle.net/1887/45885 holds various files of this Leiden University dissertation.
Author: Kersten, K. Title: Pulling the strings on anti-cancer immunity Issue Date: 2017-02-07
Pulling the strings on anti-cancer immunity
Kelly Kersten About the cover:
Based on the research described in this thesis and inspired by the song ‘Master of Puppets’ by Metallica, I envision cancer as a puppet-master restraining the protective function of the immune system. Part of my PhD work has focused on how tumor cells manipulate the function of immune cells to favor their spread throughout the body. In other words, cancer is pulling the strings on anti-cancer immunity to prevent destruction by the immune system. With the recent advances of combinatorial anti-cancer therapies (including immunomodulatory drugs) we can gain back control over the strings on anti-cancer immunity.
Cover design: Kelly Kersten & Tomasz Ahrends Artwork: Tomasz Ahrends Lay-out: Jasper Koning ([email protected]) Printing: Gildeprint, Enschede ISBN: 978-94-6233-496-0
The printing of the thesis was financially supported by the NKI-AVL. ©2016 by Kelly Kersten. All rights reserved. No part of this thesis may be reproduced, stored in a retrieval system, or transmitted in any form or by any means without prior permission of the author and the publisher holding the copyright of the articles.
The research described in this thesis was performed at the Divisions of Molecular Biology and Immunology of the Netherlands Cancer Institute – Antoni van Leeuwenhoek Hospital (NKI-AVL), Amsterdam, The Netherlands, and was supported by the Dutch Cancer Society (KWF2011-5004) and the European Research Council (InflaMet 615300). Pulling the strings on anti-cancer immunity
Proefschrift ter verkrijging van de graad van Doctor aan de Universiteit Leiden op gezag van Rector Magnificus Prof.Mr. C.J.J.M. Stolker, volgens besluit van het College voor Promoties te verdedigen op dinsdag 7 februari 2017 klokke 15.00 uur.
door Kelly Kersten
geboren te Ede in 1987 Promotores: Prof.dr. Jos Jonkers, promotor Dr. Karin E. de Visser, NKI-AVL, co-promotor
Promotiecommissie: Prof.dr. Joke Bouwstra, voorzitter Prof.dr. Meindert Danhof, secretaris Prof.dr. Ferry Ossendorp Prof.dr. Bob van de Water Prof.dr. Jacco van Rheenen (Utrecht University) Prof.dr. Jannie Borst (University of Amsterdam)
Table of contents
Chapter 1 Scope of thesis 9
Chapter 2 Genetically engineered mouse models in oncology and cancer 19 medicine EMBO Molecular Medicine, in revision.
Chapter 3 IL-17-producing γδ T cells and neutrophils conspire to promote 43 breast cancer metastasis Nature 522:345-348 (2015)
Chapter 4 Mammary tumor-derived CCL2 enhances pro-metastatic systemic 71 inflammation through upregulation of macrophage-derived IL1β In revision.
Chapter 5 Exploiting the immunomodulatory properties of chemotherapeutic 97 drugs to improve the success of cancer immunotherapy Frontiers in Immunology 6:516 (2015)
Chapter 6 Dual immune checkpoint blockade synergizes with chemotherapy in 125 a drug-dependent manner in a mouse model for de novo mammary tumorigenesis In preparation
Chapter 7 General discussion 151
Appendices English summary 171 Nederlandse samenvatting 173 Curriculum Vitae 177 List of publications 179