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Molecular Oncology & Immunology: Ton Schumacher


Ton Schumacher, Ph.D. professorGroup Leader (0.5 FTE)

About Ton Schumacher

Research interest: Cancer Immunology

The aim of our research is straightforward 1). To design novel technologies that can be used to examine and modify antigen-specific T cell immunity 2). To use these tools to unravel and manipulate the molecular processes underlying immune recognition by T lymphocytes. Within these projects, a main focus is on the design and testing of novel concepts for adoptive immunotherapy of cancer.

Dissecting antigen-specific T cell immunity in human cancer

There is now substantial evidence that therapeutic manipulation of immune reactivity can result in clinically meaningful effects on human cancer. For example, T cell responses induced by T cell checkpoint blockade, or infusion of ex vivo expanded tumor-infiltrating T cells (TIL therapy), has shown substantial activity in metastatic melanoma. Importantly, at present it is largely unknown which cytotoxic T cell reactivities mediate such cancer regressions. Furthermore, knowledge of such reactivities would be of obvious use, both to monitor current therapies and to design more targeted strategies that selectively aim to enhance immune reactivity against these antigens.

To address this issue, we have developed a broadly applicable "MHC-based toolkit" for the parallel detection of many different T cell populations within a single sample. In many ongoing projects we are now using this platform to understand the effects of for instance TIL therapy and T cell checkpoint blockade in cancer patients. 

A particularly intriguing twist to this research line is the notion that mutated 'neo-antigens' that could serve as regression antigens in patients may be identified on the basis of cancer exome data. Towards this purpose, we generate maps of all tumor-specific mutations within human cancer lesions and use this information to analyze reactivity against predicted mutated peptides by T cells from the same patient.  Interestingly, the first evidence for the feasibility of this exome-based approach to identify human neo-antigens has recently been obtained. In the coming years, this approach should offer the possibility to determine to what extent the mutational landscape in human tumors is recognized by cytotoxic T cells. In addition, this link between cancer genomics and T cell immunology may allow one to address fundamental questions about cancer immune editing, and may suggest novel ways to harness the T cell repertoire in human disease.
 (Selected references: Toebes et al., Nat Med 2006; Hadrup et al., Nat Methods 2009, Heemskerk et al., EMBO J 2012, Kvistborg et al., Curr Opin Immunol 2013, van Rooij et al., J Clin Oncol 2013)

Dissection of cellular immunity through single cell tracing

To also allow the tracing of cell fate at the single cell level, we have developed technologies with which individual cells can be tagged with genetic barcodes. This tagging technology relies on the use of oncoretroviral and lentiviral libraries containing thousands of different DNA 'barcodes'. Infection of progenitor cells of interest by these libraries of viral vectors and subsequent analysis of the barcodes present within the cell populations that arise from them can then be utilized to reveal lineage relationships. In recent projects, we have for instance used this barcode labeling strategy, together with second generation sequencing, to measure the output of individual antigen-specific T cells, and to address which (types of) progeny are generated by individual multipotent hematopoietic progenitors in vivo. In addition to this in vivo single cell tracing work, we have become highly interested in a specialized subset of tissue-resident memory T cells. In recent work we have demonstrated the existence of a population of "skin patrolling memory T cells" that cruise through former sites of infection, and in ongoing work we are evaluating how this T cell population can form a possible link between renewed antigen production and the development of a state of 'pathogen alert'.

(Selected references: van Heijst et al., Science 2009; Schumacher et al., Nat Rev immunol 2010, Ariotti et al., PNAS 2012, Gerlach et al., Science 2013, Naik et al., Nature 2013) 

Adoptive T cell therapy (collaboration with Haanen lab)

The cornerstone of our translational work is the development and evaluation of adoptive T cell therapies for human cancer. The MHC-based monitoring strategies described above form a very useful starting point for the further clinical development of TCR engineered T cell therapy, an area of research that is of special interest to the lab. In the coming years we aim to prepare for a large clinical program in which we will test the clinical value of a series of different T cell receptors that target various tumor-associated antigens. Towards this goal, we have developed technology that allows rapid TCR gene identification from many samples, and have utilized it to isolate a library of TCR genes that target many different cancer/germline antigens. In parallel work, we aim to evaluate the potential of non-viral gene transfer strategies and would like to evaluate the potential of more personalized strategies for TCR gene therapy, in which the tumor-specific TCR repertoire of individual patients is harnessed.
(Selected references: Kessels et al., Nat Immunol 2001; Bendle et al., Nat Med 2010, Linnemann et al., Nat Med 2013)


Generation of peptide MHC class I monomers and multimers through ligand exchange
Retroviral transduction of murine T cells
Spin-based transduction of human T cells


Bresser, Kasper.JPG

Kaspar Bresser

Ph.D. student


During my bachelor's (HLO at the Hogeschool Leiden) and master's (Biomedical Sciences at the University of Amsterdam) programs I received training while working in multiple labs at the LUMC, NKI and Whitehead Institute. During these internships I worked on various projects in the fields of tumor immunology, gene regulation and bioengineering.

My current research focuses on two subjects. First, to dissect the recognition of tumor cells by T cells, mainly from the tumor cell perspective. Second, to develop and engineer systems that allow one to address various subjects in tumor biology and immunology.

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Marjolein de Bruijn



After finishing my study 'Biology and Medical Laboratory Research' at the Hogeschool Leiden (BASc), I started working as a technician in the group of Ton Schumacher where I investigated cell death mechanisms induced after T cell recognition. Currently, I am working on more translational research questions by using ex vivo models to assess the effects of immunotherapies on different types of human cancers.

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Dijkgraaf, Feline 2

Feline Dijkgraaf MSc

Ph.D. student


After finishing the broad Bachelor Bèta-gamma, I enrolled in the Master Biomedical Sciences at the University of Amsterdam. During this training, I specifically focused on cancer immunology at various research institutes such as the University of Cambridge, UK, the Amsterdam Medical Center and finally the Netherlands Cancer Institute (NKI-AVL). 

Currently, I am working on a PhD-project in the stimulating work environment of the NKI-AVL, in which I aim to study the behavior of tissue-resident memory T cells using live imaging. 

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Mirjam Hoekstra MSc

Ph.D. student


I studied Life Science (Bio-exact, BSc) and Immunology (MSc) at the University of Amsterdam. During my studies, I performed research internships at the Netherlands Cancer Institute, Utrecht University and Massachusetts Institute of Technology, focusing on innate and adaptive immunity.

I am mostly interested in fundamental immunology, specifically the role of T cells in immune responses. I have been working in the Schumacher lab as a PhD student since February 2014, and my work focuses on the behavior of tissue-resident memory T cells in the skin and the development of (reporter) technologies to study this.

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Anne van der Leun MSc

Ph.D. student


After finishing my Master "Cancer Genomics and Developmental Biology" at Utrecht University, I joined the Schumacher and Zuur labs as a PhD student in June 2015. Here, my focus is to dissect T cell reactivity in human cancer. I aim to better understand the functionality of tumor infiltrating lymphocytes at the single cell level, with the ultimate goal to improve current immunotherapeutic approaches and make immunotherapy applicable to a broader range of tumor types. 

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Logtenberg, Meike

Meike Logtenberg MSc

Ph.D. Student


After finishing my Bachelor's degree at University College Utrecht, I enrolled in the 'Cancer, Stem Cells and Developmental Biology' Master program at the Utrecht University. During this program, I was trained at the Hubrecht Institute (Utrecht) and at the Centre of Stem Cells and Regenerative Medicine (London) in cancer and stem cell biology. I started my PhD at the group of Ton Schumacher in October 2015. I am interested in identifying and understanding tumor escape mechanisms from the immune system, and how these mechanisms can be targeted to improve effective tumor cell killing.

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Sahillioglu, Ali Can.JPG

Ali Can Sahillioglu

Ph.D. Student


The rate of scientific progress is limited by scientists' imagination, and their research tools. My research interest is to develop novel methods for single cell tracing and then use these to reveal the underlying mechanisms of cellular heterogeneity in T-cell populations and cancer.

I received my B.Sc. and M.Sc. degrees from Bogazici University, Istanbul, and I have been working in the Schumacher Lab since October 2013.

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Slagter, Maarten

Maarten Slagter

Ph.D. student


I investigate the interaction between adaptive immunity and developing and established tumors using clinical and -omics data. The end goal is an interpretable, quantitative model of patient response to various immunotherapies.

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Thommen, Daniela

Dr. Daniela Thommen

Senior Postdoctoral Fellow


After finishing my medical studies, I did my PhD in the field of T cell immunology. After my residency in internal medicine, I completed my training in medical oncology and worked in parallel as a postdoc in cancer immunology at the University Hospital Basel. A Swiss National Science Foundation fellowship allowed me to join the Schumacher lab in May 2016. The focus of my research is (a) to achieve a better understanding of how intratumoral heterogeneity in dysfunctional T cells influences the outcome to immunotherapy and (b) to develop novel models to visualize the effects of immunotherapy in human cancers.

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Mireille Toebes

Research Technician


In September 1996, I started as a technician in the lab of Ton Schumacher: setting up the lab was a challenging job. During the following years, I developed my own projects, specializing myself in protein biochemistry, and in particular MHC multimer-based  tools for immune monitoring (Toebes et al, Nat Med. 2006).  In addition to this work, currently  I am training and assisting technicians, post-docs and PhD students, and have collaborations with groups in other disciplines, such as chemistry. This variation makes this job exciting: I can express my creative mind.

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Jos Urbanus

Research Technician


In 2001 I joined the Schumacher lab as a technician and since then I worked on several challenging projects (not all of them equally successful). A large part of my job is to design constructs and cloning strategies, of which the creation of the barcode mouse certainly was the most ambitious cloning project I was ever involved in. At the moment I am also managing the barcode mouse project. Over the years I have acquired quite some experience in developing gene designs and am now helping out many people in their efforts (as a one-eyed king in the land of the blind..)

Most of all I like the diversity in the research projects and the great support there is among colleagues.

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Key publications View All Publications

  • Glutaminyl cyclase is an enzymatic modifier of the CD47- SIRPα axis and a target for cancer immunotherapy.

    Nat Med. 2019 Apr;25(4):612-619.

    Logtenberg MEW, Jansen JHM, Raaben M, Toebes M, Franke K, Brandsma AM, Matlung HL, Fauster A, Gomez-Eerland R, Bakker NAM, van der Schot S, Marijt KA, Verdoes M, Haanen JBAG, van den Berg JH, Neefjes J, van den Berg TK, Brummelkamp TR, Leusen JHW, Scheeren FA, Schumacher TN.

    Link to Pubmed
  • Dysfunctional CD8 T Cells Form a Proliferative, Dynamically Regulated Compartment within Human Melanoma.

    Cell. 2019 Feb 7;176(4):775-789.e18.

    Li H, van der Leun AM, Yofe I, Lubling Y, Gelbard-Solodkin D, van Akkooi ACJ, van den Braber M, Rozeman EA, Haanen JBAG, Blank CU, Horlings HM, David E, Baran Y, Bercovich A, Lifshitz A, Schumacher TN, Tanay A, Amit I.

    Link to Pubmed

Recent publications View All Publications

  • Defining 'T cell exhaustion'.

    Nat Rev Immunol. 2019 Sep 30.

    Blank CU, Haining WN, Held W, Hogan PG, Kallies A, Lugli E, Lynn RC, Philip M, Rao A, Restifo NP, Schietinger A, Schumacher TN, Schwartzberg PL, Sharpe AH, Speiser DE, Wherry EJ, Youngblood BA, Zehn D.

    Link to Pubmed
  • Loss of p53 triggers WNT-dependent systemic inflammation to drive breast cancer metastasis.

    Nature. 2019 Aug;572(7770):538-542.

    Wellenstein MD, Coffelt SB, Duits DEM, van Miltenburg MH, Slagter M, de Rink I, Henneman L, Kas SM, Prekovic S, Hau CS, Vrijland K, Drenth AP, de Korte-Grimmerink R, Schut E, van der Heijden I, Zwart W, Wessels LFA, Schumacher TN, Jonkers J, de Visser KE.

    Link to Pubmed


  • Office manager

    Stephanie Timmer

  • E-mail

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    +31 20 512 2099


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