Cover Page
The handle
http://hdl.handle.net/1887/139165
holds various files of this Leiden
University dissertation.
Author: Melssen, M.M.
Title: Overcoming barriers to T cell activation, infiltration and function in tumors
Issue date: 2021-01-26
Overcoming barriers to T cell activation, infiltration
and function in tumors
© Marit Melssen, Leiden, the Netherlands
Overcoming barriers to T cell activation, infiltration and function in tumors All rights reserved. No part of this thesis may be reproduced or transmitted in any form, by any means, electronic or mechanical, without prior permission of the author, or where appropriate, of the published of the articles.
The research presented in this thesis was performed at the Department of Microbiology, Immunology and Cancer Biology and the Department of Surgery at the University of Virginia.
Financial support for the research and publication of the work in this thesis was kindly provided by: National Institutes of Health, Cancer Research Institute, GlaxoSmithKline, Alice and Bill Goodwin, Rebecca C. Harris Fellowship and the Commonwealth Foundation for Cancer Research.
Cover design Sydna Mundy Layout by Loes Kema
Printed by GVO drukkers & vormgevers B.V. ISBN 978-94-6332-721-3
Overcoming barriers to T cell activation, infiltration
and function in tumors
Proefschrift
Ter verkrijging van de graad van Doctor aan de Universiteit Leiden,
op gezag van de Rector Magnificus prof. Mr. C.J.J.M. Stolker, volgens besluit van het College voor Promoties
te verdedigen op dinsdag 26 januari, klokke 15:00 uur
door
Marit Melssen
Geboren te Helmond, Nederland in 1990
Promotor: Prof. Dr. S.H. van der Burg Co-promotoren: Prof. Dr. C.J.M. Melief
Prof. Dr. V.H. Engelhard (University of Virginia, USA) Leden promotiecommissie: Prof. Dr. J.B.A.G. Haanen
Prof. Dr. T.D. de Gruijl
(Vrije Universiteit, Amsterdam) Prof. Dr. J.E.M.A. Debets
I shot an arrow into the air, It fell to earth, I knew not where;
For, so swiftly it flew, the sight Could not follow it in its flight. I breathed a song into the air, It fell to earth, I knew not where; For who has sight so keen and strong,
That it can follow the flight of song? Long, long afterward, in an oak I found the arrow, still unbroke; And the song, from beginning to end,
I found again in the heart of a friend.
Henry Wadsworth Longfellow
CONTENTS
Chapter 1 General Introduction 9
Chapter 2 Vaccines targeting helper T cells for cancer
immunotherapy 31
Chapter 3 A multipeptide vaccine plus toll-like receptor agonists LPS or polyICLC in combination with incomplete Freund’s adjuvant in melanoma patients
49
Chapter 4 Characterization and comparison of innate and adaptive immune responses at vaccine sites in melanoma vaccine clinical trials
83
Chapter 5 Formation and phenotypic characterization of CD49a, CD49b and CD103 expressing CD8 T cell populations in human metastatic melanoma
111
Chapter 6 Differential expression of CD49a and CD49b determines localization and function of tumor infiltrating CD8 T-cell subpopulations
133
Chapter 7 Discussion 169
Chapter 8 Nederlandse samenvatting 189
Acknowledgements 193
List of Publications 195
