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Tumor Biology & Immunology: Jannie Borst

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Jannie Borst, Ph.D. professorGroup leader

About Jannie Borst

Research interest: Deciphering molecular mechanisms that govern the T cell response

Most research activities of Jannie Borst's group have been transferred to the LUMC from July 1, 2019.

Our work is in the first place inspired by the desire to improve immunotherapy of cancer. Sustaining survival and memory function of T cells is expected to improve anti-tumor immunity. At the same time, mechanisms we elucidate may be exploited to improve vaccination against infectious disease and to block undesired immune responses, as in auto-immunity and transplant rejection. This work is carried out in vivo in mouse models and in matching cellular systemsin vitro, whereby we presently focus on interactions between T cells and dendritic cells. We collaborate with biotech industry to validate therapeutic antibodies. A second aim is to explore the concept of "immunogenic cell death" in the context of radio- or chemo-immunotherapy. In this work, we combine our expertise on T cell- and dendritic cell function with our expertise on apoptosis signaling. This work is done for a large part in cell modelsin vitro, using biochemical and cell biological approaches. The link between basic cell biology and clinical practice is made by studies in mouse tumor models. In this translational work, we collaborate with the Division of Radiotherapy.

Key contributions

● Discovery of the CD3 gamma, delta and epsilon subunits of the human T cell receptor/CD3 complex.

● Discovery of a novel human T-cell lineage expressing T-cell receptor gamma/delta. Collaboration with other groups allowed us to identify T cell receptor gamma/delta by biochemical means. Independent work led to the generation and diagnostic use of the first antibody that could identify cells expressing T cell receptor gamma/delta in human blood and tissues.

● Discovery of the signal transduction complex associated with human membrane immunoglobulin, alias the B cell antigen receptor (BCR, a term coined by our group).

● Implication of various signaling molecules in the BCR pathway, including Btk, c-Cbl and its mechanism of action.

● Identification of TNF receptor family member CD27 and its ligand CD70 as an important T cell costimulatory system, critical for the generation of effector and memory T cells.

● Elucidation of the mechanism underlying ceramide production in response to apoptotic stimuli.

● Discovery of a novel mechanism of ubiquitination that regulates apoptosis signaling by death receptors.

Co-workers

Experience

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Inge Verbrugge

Senior scientist

Experience

My research is focused on improving the therapeutic effect of localized radiotherapy using highly specific compounds (antibodies) that stimulate cells of the immune system, a treatment called 'radio-immunotherapy'.During my post-doc time at the Peter MacCallum Cancer Centre inMelbourne,Australia, we have shown that radio-immunotherapy could cure mice bearing established mammary (breast) tumours. At the moment, I am continuing this work at the NKI in two main projects: (1) Investigating the potential of radio-immunotherapy in highly relevant mouse models of melanoma and (2) Investigating the cellular and molecular mechanism that underlie the response to radio-immunotherapy.

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Haar Avila, Irene van der

Irene van der Haar Avila

Technician

Experience

In 2018, I obtained my master's degree in Molecular Life Sciences at the Radboud University of Nijmegen. During my studies, I performed an internship in the laboratory of Harry Dolstra at the Radboudumc, followed by an internship in the group of Rolf Kiessling at the Karolinska Institute in Stockholm. Currently, I'm working as a technician in the group of Dr. Inge Verbrugge and Prof. Jannie Borst. Our main focus is to enhance the antitumor effects of localized radiotherapy in combination with immunotherapy by stimulating the T cell response.

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de Wit

Tom de Wit

Technician

Experience

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Frijlink

Elselien Frijlink

Ph.D. Student

Experience

In November 2015 I finished the master program "Infection and Immunity" at Utrecht
University, for which I performed an internship in the laboratory of Jürgen
Kuball at UMC Utrecht, followed by an internship in the lab of Martin Blaser at
NYU in New York. Following my graduation I worked in the Neuro-Oncology
department at UMC Utrecht where I aimed to induce a potent CD4 T-cell response
against gliomas.
My PhD project is focused on making radiotherapy locally more effective and systemically
active, by rational interventions that stimulate the cytotoxic T cell response,
an approach termed 'radio-immunotherapy'.

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Volkov

Andriy Volkov

Ph.D. Student

Experience

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Key publications View All Publications

  • CD4+ T cell help confers a cytotoxic T cell effector program including coinhibitory receptor downregulation and increased tissue invasiveness.

    Immunity 47: 848-861, 2017.

    Ahrends, T., Spanjaard, A., Pilzecker, B., Bąbała, N., Bovens, A., Xiao, Y., Jacobs, H., and Borst, J.

    Link to pubmed
  • CD4+ T-cell help in cancer immunology and immunotherapy.

    Nat Rev Immunol. 2018 Jul 29.

    Borst, J., Ahrends, T., Bąbała, N., Melief, C.J., and Kastenmuller, W.

    Link to pubmed
 
 

Recent publications View All Publications

  • Subcellular localization of antigen in keratinocytes dictates delivery of CD4+ T cell help for the CTL response upon therapeutic DNA vaccination into the skin

    Cancer Immunol Res. 2018 Jul;6(7):835-847

    Bąbała N, Bovens A, de Vries E, Iglesias-Guimarais V, Ahrends T, Krummel MF, Borst J*, and Bins AD*. *Equal contribution

    link to pubmed
  • Quantitative proteomics reveals a unique wiring of signaling pathways that defines human regulatory T cell identity

    Immunity. 2018 May 15;48(5):1046-1059

    Cuadrado, E., van den Biggelaar, M*., de Kivit, S*., Chen, Y.-Y., Slot, M., Doubal, I., Meijer, A., van Lier, R.A.W., Borst, J.*, and Amsen D.A*. *Equal contribution

    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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