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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

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Pulling the strings on anti-cancer immunity

Kelly Kersten

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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 (koningjj@gmail.com) 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).

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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

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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)

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Chapter 1 Chapter 2

Chapter 3

Chapter 4

Chapter 5

Chapter 6

Chapter 7 Appendices

Scope of thesis

Genetically engineered mouse models in oncology and cancer medicine

EMBO Molecular Medicine, in revision.

IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis

Nature 522:345-348 (2015)

Mammary tumor-derived CCL2 enhances pro-metastatic systemic inflammation through upregulation of macrophage-derived IL1β In revision.

Exploiting the immunomodulatory properties of chemotherapeutic drugs to improve the success of cancer immunotherapy

Frontiers in Immunology 6:516 (2015)

Dual immune checkpoint blockade synergizes with chemotherapy in a drug-dependent manner in a mouse model for de novo mammary tumorigenesis

In preparation General discussion English summary

Nederlandse samenvatting Curriculum Vitae

List of publications

9 19

43

71

97

125

151 171 173 177 179

Table of contents

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