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Tumor Biology & Immunology: Karin de Visser

KarinDeVisser.jpg

Karin de Visser, Ph.D. professorGroup Leader

About Karin de Visser

Research interest: Inflammation and Cancer

Impact of the immune system on metastatic breast cancer and therapy response

Cancer metastasis formation and unresponsiveness to conventional therapies are the challenges in cancer therapy that most urgently need solutions. The overall goal of our research is to understand by which mechanisms the immune system impacts on breast cancer metastasis and therapy response. Through mechanistic understanding of the crosstalk between the immune system and cancer, we aim to contribute to the design of novel immunomodulatory strategies to fight metastatic breast cancer and to increase the efficacy of conventional anti-cancer therapies.

Dissecting the impact of the immune system on metastatic breast cancer

Metastatic disease accounts for over 90% of breast cancer-related deaths. Crosstalk between cancer cells and immune cells reportedly influences metastasis formation. However, the impact of the immune system on the complex metastatic cascade is poorly understood and both tumor-protective and tumor-promoting properties have been reported. To mechanistically elucidate how immune cells affect metastasis, we have established a novel pre-clinical model of spontaneous breast cancer metastasis that mimics the clinical course of metastatic disease in humans. Using genetic, biological and pharmacological strategies, we assess the influence of immune cells and inflammatory mediators on multi-organ metastasis formation. We have recently discovered that breast tumors maximize their chance to metastasize by evoking a systemic inflammatory cascade involving T cells and neutrophils. The goal of our current studies is to mechanistically dissect the pathways leading to cancer-initiated activation of systemic pro-metastatic inflammatory responses, and to elucidate how systemic inflammation facilitates metastasis. In the longer term, these studies may contribute to the rational design of novel strategies that target inflammatory pathways to fight metastasis. 

Elucidating the impact of the immune system on the efficacy of anti-cancer therapies

One of the major impediments to effective cancer therapy is acquisition of unresponsiveness to cytotoxic effects of anti-cancer therapy regimens. An increasing body of literature now suggests that cancer cell extrinsic processes, such as inflammatory responses and cytokines, are involved in regulating the efficacy of anti-cancer therapies. Using invivotumor models that faithfully recapitulate human breast tumorigenesis and spontaneous metastasis formation, we aim to understand the mechanisms by which myeloid cells counteract the efficacy of conventional anti-cancer therapies, and to dissect the deleterious feedback mechanisms within the immune system upon treatment with immunomodulatory therapies. Ultimately, our studies may contribute to the design of immunomodulatory strategies to increase the efficacy of conventional anti-cancer therapies.

Co-workers

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Noor Bakker

Ph.D. student

Experience

I studied Biomolecular Sciences at the VU Amsterdam. After obtaining my master's degree, I worked for 5 years as a technician in the GMP therapeutic production facility of the NKI were we produced e.g. TILs. In addition, I was involved in several translational research projects in collaboration with the groups of Ton Schumacher and John Haanen, and responsible for the immunomonitoring of a phase I/II clinical vaccination trial.

I am currently a PhD student in the lab of Karin de Visser, in close collaboration with Marleen Kok. My research project is focused on assessing the influence of tumor subtype, tumor stage and (immuno)therapy response on the intratumoral and systemic immune landscape of breast cancer patients.

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Blomberg, Olga

Olga Blomberg, MSc

Ph.D. student

Experience

After obtaining my bachelor's degree at Amsterdam University College, I continued my studies in oncology and immunology in the Biomedical Sciences Master at the UvA. I was trained at the NKI in the lab of Heinz Jacobs studying DNA damage tolerance, and in the lab of Hidde Ploegh at the Whitehead Institute for Biomedical Research where I studied the requirements of effective cancer immunotherapy using alpaca-derived heavy chain-only nanobodies. In May 2017, I joined the lab of Karin de Visser to study tumor-associated immunosuppressive mechanisms to enhance the success of immunotherapy for metastatic breast cancer.

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Duijst, Maxime

Maxime Duijst

Technician

Experience

I obtained my General Biology bachelor's degree at the University of the District Columbia, Washington DC, followed by completing the master 'Infection & Immunity" at Utrecht University, Utrecht in 2018.

Throughout 2018, I worked at the National Institute of Health (RIVM) working on several projects concerning lung diseases by developing B cell and T cell assays, mainly using flow cytometry.

As my research interest is very broad, I joined the project of Karin de Visser and Marleen Kok in February 2019 to study the relationship between, and the effect of the combination of chemotherapy with checkpoint inhibition, on suppressive immune cells and cancer cells isolated from metastatic breast cancer patients.

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Duits

Danique Duits

Ph.D. student

Experience

After I obtained my Bachelor's degree in 2015, I continued with the Master Biomedical Sciences at Leiden University. During this Master, I focused on oncology by following the specialization "Cancer Pathogenesis and Therapy". My first internship took place at the LUMC in the lab of Prof. dr. Henri Versteeg, where I focused on breast cancer-associated thrombosis. I joined the lab of Karin de Visser at the NKI for my final internship studying the effect of p53 loss on systemic inflammation in breast cancer, and to write my master thesis about immature myeloid cells in inflammation and cancer. 

In October 2017, I continued working in the lab of Karin de Visser as a Ph.D. student to study the role of the genetic make-up of breast tumors in cancer-associated inflammation and metastatic disease.

 

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Dyk van

Ewald van Dyk

Postdoctoral Fellow

Experience

I obtained a bachelor's degree in electrical engineering and a master's in computer engineering, focusing on theoretical pattern recognition. I did my PhD in computational biology at the Delft University of Technology specializing in DNA copy number analysis in diverse cancer types with Lodewyk Wessels as my main promotor. Afterwards, I did a postdoc in adaptive immunity (computational prediction of T-cell receptor ligands) at the University of Utrecht under Can Kesmir.

In October 2018 I joined the group of Karin de Visser, where we seek to gain a mechanistic understanding on how breast cancer effects the systemic immune milieu.

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Garner, Hannah

Hannah Garner

Postdoctoral fellow

Experience

I did my PhD in the lab of Prof. Frederic Geissmann at King's College London where I studied myelopoiesis with a particular focus on patrolling monocyte development. I joined Karin de Visser's lab in August 2016 as a postdoctoral researcher to investigate the impact of inflammation on breast cancer metastasis and I am particularly interested in the mechanisms through which neutrophils facilitate metastasis establishment.

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Tisee Hau

Technician

Experience

I studied Biology and Medical Laboratory Research in Leiden.

I joined the Karin de Visser Lab in February 2008 to work on the role of the adaptive immune system during breast cancer formation.

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Klaver, Chris

Chris Klaver

Technician

Experience

In November 2018 I joined a project of Karin de Visser and Marleen Kok to analyze immune suppressive cascades in metastatic breast cancer patients and see how these cascades affects the effector immune cells and the success of immune checkpoint blockade.

During my bachelor I developed a strong interest in oncology so I started the master Oncology at the VU Amsterdam. I was trained at the NKI in the lab of prof. Gerrit Meijer, exploring utility of liquid biopsies for colorectal cancer. Afterwards, I did my internship at prof. Maria Rescigno's lab in Milan, where we analyzed the role of bacteria in the metastatic process of colorectal and breast cancer.

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Kos, Kevin

Kevin Kos

Ph.D. student

Experience

Due to a strong interest in oncology and immunology, I started the master Oncology at the VU after completion of the bachelor Biomedical Sciences. During this master, I was trained at the NKI in the group of Emiel Voest and at the Brisbane QIMR Berghofer institute in the group of Mark Smyth, where I focused on the role of heparanase in NK cells for my thesis. After receiving the NWO Diamond grant in cooperation with the de Visser Lab, I was given the opportunity to start my PhD in October 2016 on the role of Tregs in breast cancer metastasis

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Laine, Anni

Anni Laine

Postdoctoral Fellow

Experience

I obtained my PhD degree in the laboratory of Prof. Jukka Westermarck at Turku Centre for Biotechnology at University of Turku, Finland. During my PhD training I investigated the in vivo role of the recently identified oncoprotein CIP2A in breast cancer. After finishing my PhD I focused on studying cellular mechanisms promoting formation of the most aggressive breast cancer subtype, basal-like breast cancer.

In April 2016 I joined Dr. Karin de Visser's laboratory to investigate novel approaches to target basal-like breast cancer. My research focus is on understanding the crosstalk between senescent tumor cells and tumor infiltrating immune cells.

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Raeven

Lisanne Raeven

Technician

Experience

I studied Medical Biology at Radboud University in Nijmegen where I specialized in clinical biology. During my master internship at the Laboratory of Pediatric Infectious Diseases at Radboud UMC I investigated the effect of RSV on the immune system in adults and neonates, focusing on T cells. 

In May 2018 I joined the Karin de Visser group to work as a research technician and investigate the relation between myeloid cells and their mediators and chemo therapy responsiveness in breast cancer.

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Camilla Salvagno, MSc

Ph.D. student

Experience

I obtained my master's degree in "Medical Molecular and Cellular Biotechnology" at San Raffaele University inMilan,Italy. I performed my master's internship in Dr. Angela Gritti's lab at the Telethon Institute for Gene Therapy San Raffaele Institute, Milan) where my project was aimed at the development of an in vivo gene therapy approach for the treatment of Globoid Cell Leukodystrophy, a neurodegenerative disorder.

In February 2013, I joined Dr. Karin de Visser's group as a Ph.D. student to investigate the role of myeloid cells and their mediators in chemotherapy responsiveness of breast cancer.

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Spagnuolo, Lorenzo

Lorenzo Spagnuolo

Postdoctoral fellow

Experience

I did my PhD in the lab of Carole Bourquin at the Univerisity of Fribourg in Switzerland, where I studied mechanisms of T lymphocyte migration in tumor and mucosal tissue. I joined the group of Karin de Visser in May 2017 as a postdoctoral scientist, on a Swiss National Science Foundation fellowship.
My current research aims to understand how chemotherapy influences T lymphocyte dysfunction induced by de novo mammary tumorigenesis.

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Kim Vrijland

Technician

Experience

I studied Biology and Medical Laboratory Research in Leiden  from 2005 - 2008 and completed the Master Oncology in 2010 at the Free University in Amsterdam.

From January 2011 - March 2013 I worked for Immunaffect at the department of Molecular Cell Biology and Immunology (MCBI) at  the Free University Medical Centre in the group of Prof. Dr. G. Kraal. I worked on the development of bi- specific antibodies for the treatment of auto- immune diseases.

I joined the Karin de Visser's group in March 2013 to study the role of the inflammatory tumor microenvironment in breast cancer development, metastasis and chemotherapy.

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Wellenstein, Max.JPG

Max Wellenstein, MSc

Ph.D. student

Experience

I studied Biology at Utrecht University and obtained my MSc. degree in Cancer Genomics and Developmental Biology in 2014. My first research internship took place in the Knipscheer lab at the Hubrecht Institute, where I worked on DNA interstrand crosslink repair. For my second internship, I was awarded several grants (KWF, Dr. Hendrik Muller foundation, K.F. Hein foundation) to join the Mittal lab at Weill Cornell Medical College in New York. At this lab I studied the contribution of tumor- and myeloid cell-derived MMP14 on lung cancer progression.

In October 2014, I joined Karin de Visser's lab as a Ph.D. student to investigate the impact of tumor-associated neutrophils on metastatic breast cancer.   

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Weverwijk

Antoinette van Weverwijk

Postdoctoral Fellow

Experience

I did my PhD in the lab of Prof. Clare Isacke at the Institute of Cancer Research in London, where I performed an in vivo shRNA screen and identified AKR1B10 as a novel driver of breast cancer metastasis.

I joined Karin de Visser's lab in March 2018 as a postdoctoral researcher. I'm currently working on two research projects. In the first project I'm trying to understand how tumour-associated myeloid cells counteract chemotherapy response. The second project is focused on identifying tumour-genotype/immune-phenotype relationships in breast cancer, with a particular interest in PI3K alterations.

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Research updates View All Updates

  • Vici Grant for Karin de Visser

    Karin de Visser, group leader Tumour Biology & Immunology, has been awarded a Vici Grant by the Netherlands Organisation for Scientific Research (NWO), to decipher how breast tumors shape their immune landscape.

    Link to article
  • Targeting macrophages helps chemotherapy succeed

    In an online publication in Nature Cell Biology, Camilla Salvagno from Karin de Visser's group and other researchers revealed how targeting intratumoral macrophages enhances the efficacy of platinum-based chemotherapy in a preclinical mouse model for breast cancer.

    Link to article

Key publications View All Publications

  • Therapeutic targeting of macrophages enhances chemotherapy efficacy by unleashing type I interferon response.

    Nat Cell Biol. 2019 Apr;21(4):511-521.

    Salvagno C, Ciampricotti M, Tuit S, Hau CS, van Weverwijk A, Coffelt SB, Kersten K, Vrijland K, Kos K, Ulas T, Song JY, Ooi CH, Rüttinger D, Cassier PA, Jonkers J, Schultze JL, Ries CH, de Visser KE.

    Link to PubMed
  • IL-17-producing γδ T cells and neutrophils conspire to promote breast cancer metastasis.

    Nature doi: 10.1038/nature14282 (2015)

    Coffelt SB, Kersten K, Doornebal CW, Weiden J, Vrijland K, Hau CS, Verstegen NJ, Ciampricotti M, Hawinkels LJ, Jonkers J, de Visser KE et al.

    Link to pubmed
 
 

Recent publications View All Publications

  • Sticking together helps cancer to spread.

    Nature. 2019 Feb;566(7745):459-460.

    Egeblad M, de Visser KE.

    Link to PubMed
  • Cancer-Cell-Intrinsic Mechanisms Shaping the Tumor Immune Landscape.

    Immunity. 2018 Mar 20;48(3):399-416.

    Wellenstein MD, de Visser KE.

    Link to PubMed
 

Contact

  • Office manager

    Karin van der Heijden

  • E-mail

    k.vd.heijden@nki.nl

  • Telephone Number

    +31 20 512 2055

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