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Immunology: 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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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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Chris Doornebal, M.D.

Ph.D. student

Experience

I studied Medicine and Philosophy at theRadboudUniversityinNijmegen. After my graduation in 2008, I became a resident in Anesthesiology at the Academic Medical Center (AMC)/UniversityofAmsterdam. In July 2009, I joined the De Visser laboratory as a PhD student to participate in a research project which mainly focuses on mechanisms involved in breast cancer metastasis formation and seeks to identify novel therapeutic targets to treat or prevent metastatic disease. My PhD training forms an integral part of my clinical training to become an anesthesiologist and is therefore co-supervised by prof. dr. M.W. Hollmann (AMC,Amsterdam).

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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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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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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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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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Kos, Kevin

Kevin Kos

PhD 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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Research updates View All Updates

  • 2015 Metastasis Prize of the Beug Foundation for Metastasis Research

    Karin de Visser was awarded the 2015 Metastasis Prize for advanced researchers of the Beug Foundation for Metastasis Research (March 30, 2015).

     

    Link to article
  • How immune cells facilitate the spread of breast cancer

    The body's immune system fights disease, infections and even cancer, acting like foot soldiers to protect against invaders and dissenters. But it turns out the immune system has traitors amongst their ranks. Dr. Karin de Visser and her team at the Netherlands Cancer Institute discovered that certain immune cells are persuaded by breast tumors to facilitate the spread of cancer cells. Their findings are published advanced online on March 30 in the journal Nature.

    Link to press release

Key publications View All Publications

  • 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 et al.

    Link to pubmed
  • Neutrophils in cancer: neutral no more

    Nature Reviews Cancer (2016)

    Seth B. Coffelt, Max D. Wellenstein, Karin E. de Visser

    Link to publication
 
 

Recent publications View All Publications

  • How neutrophils promote metastasis. Neutrophils may be cellular targets for cancer therapy

    Science 8 April 2016

    Summary: http://science.sciencemag.org/cgi/content/summary/352/6282/145?ijkey=nRb8EufSVQu3Y&keytype=ref&siteid=sci

    Link to website:
  • Exploiting the immunomodulatory properties of chemotherapeutic drugs to improve the success of cancer immunotherapy.

    Front. Immunol. 2015;6:516.

    Kersten K, Salvagno C, de Visser KE.

    Link to pubmed
 

Contact

  • Office manager

    Renske Muns-de Jong

  • E-mail

    rm.d.jong@nki.nl

  • Telephone Number

    +31 20 512 2055

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