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Molecular Oncology & Immunology: Pia Kvistborg, Ph.D.

Kvistborg, Pia

Pia Kvistborg, Ph.D.Junior Group Leader

About Pia Kvistborg

Research interest: Cancer Immunology

Importantly, in spite of the recent major successes of immunotherapy, only part of the treated patients responds to therapy and many patients relapse after initial responsiveness. It is likely that in some cases such resistance is caused by tumor cell-intrinsic properties (e.g. loss of MHC expression or lack of antigens). However, differences in the level of T cell (dys)functionality between patients (and malignancies) is likely to form a second factor.  Because of this, we consider it plausible that patients that are unresponsive to current immunotherapy strategies could benefit from novel combination strategies, including both different types of combination immunotherapy, but also combinations of immunotherapies with conventional therapy. To allow this, it is of key importance to understand how the T cell compartment is composed in different malignancies, and how different anti-cancer therapies influence this T cell compartment.

The overall goal of the Kvistborg lab is to understand how anti-cancer therapies influences tumor-specific T cells. The key therapies we are investigating are 1) checkpoint targeting therapies, a still novel class of anti-cancer drugs that with recent major clinical success have entered center stage in oncology; and 2) conventional therapy, such as chemotherapy, that is standard of care for a high number of malignancies, and of which it is well possible that part of its effect is mediated via T cell immunity.

Checkpoint targeting therapies

Checkpoint targeting therapies, in particular anti-PD-1, have recently reached center stage in oncology treatment. Clinical trials with anti-PD-1 and anti-PD-L1 antibodies have already shown objective responses in multiple malignancies. However, in spite of these recent major successes, the number of long-term survivors still remains limited and many patients do not respond or relapse after initial responsiveness. Importantly, this new class of drugs causes serious adverse events in up to half of treated patients. Because of these limitations, the discovery of T cell signatures and biomarkers that can predict whether tumor-specific T cells will be re-activated by this therapy will be important to help understand which patients are most likely to benefit. While it is likely that in some cases therapy resistance is caused by tumor cell-intrinsic properties, recent data in lung cancer suggest that unresponsiveness can also be due to varying levels of T cell exhaustion. We are assessing the qualitative changes in tumor-specific T cells that are caused by checkpoint targeting therapy. 

Conventional anti-cancer therapies

Chemotherapy is first line standard of care for the vast majority of malignancies. Tumor regression based on this type of therapy can result in release of tumor antigens, disruption of the tumor structure and alterations the composition of the tumor microenvironment potentially making the tumor more 'visible' to the immune system. Furthermore, in a recent study it was shown that standard of care chemotherapy (carboplatin and paclitaxel) for cervical cancer patients resulted in an increase in virus-specific T cells, and importantly, increased proliferative capacity of the T cells. This effect may at least in part be due to depletion of immune suppressive cell subsets including myeloid derived suppressor cells. These findings strongly indicate that chemotherapy can influence the quality of T cells and it is crucial to understand what qualitative alterations chemotherapy can have on the clinically relevant T cells, and what classes of chemotherapeutic drugs that may have such an effect.

Co-workers

Gangaev, Anastasia

Anastasia Gangaev

Ph.D. Student

Experience

I completed my bachelor studies in Molecular Biology at the JGU (Mainz, Germany). During that time, I worked as a student assistant at the BionTech AG (Mainz) where I gained in depth insights into the development of cancer immune therapeutics. In 2016, I obtained my master's degree in Biomedical Science with the focus on Advanced Microscopy and Cell Biology at the UvA. My strong interest in cell biology and cancer immunology led to my training as an intern at the Karolinska Institutet (Stockholm), Sanquin and the NKI.

In October 2016, I started my PhD in the newly established group of Pia Kvistborg. Our aim is to investigate how cancer therapies such as checkpoint blockade or chemotherapy alter the quality of tumor specific T cells in patients.

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Philips, Daisy.jpg

Daisy Philips, MSc

Technician

Experience

After finishing my Master at the Free University of Amsterdam, I started working as a technician in the group of Ton Schumacher. The main focus of my work is the immunomonitoring of patients who received immunotherapy. This involves the analysis of patient material by combinatorial coding for the detection of tumor reactive T cells and the analysis of patient material to assess the functionality of tumor reactive T cells.

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Key publications View All Publications

  • Anti-CTLA-4 therapy broadens the melanoma-reactive CD8+ T cell response.

    Sci Transl Med. 2014 Sep 17;6(254)

    Kvistborg P, Philips D, Kelderman S, Hageman L, Ottensmeier C, Joseph-Pietras D, Welters MJ, van der Burg S, Kapiteijn E, Michielin et al.

    Link to pubmed
  • Tumor exome analysis reveals neoantigen-specific T-cell reactivity in an ipilimumab-responsive melanoma.

    J Clin Oncol. 2013 Nov 10;31(32):e439-42.

    van Rooij N, van Buuren MM, Philips D, Velds A, Toebes M, Heemskerk B, van Dijk LJ, Behjati S, Hilkmann H, El Atmioui D, Nieuwland M, et al.

    Link to pubmed
 
 

Recent publications View All Publications

  • Thinking outside the gate: single-cell assessments in multiple dimensions.

    Immunity. 2015 Apr 21;42(4):591-2.

    Kvistborg P, Gouttefangeas C, Aghaeepour N, Cazaly A, Chattopadhyay PK, Chan C, Eckl J, Finak G, Hadrup SR, Maecker HT, Maurer D, Mosmann...

    Link to pubmed
  • pMHC Multiplexing Strategy to Detect High Numbers of T Cell Responses in Parallel.

    Methods Mol Biol. 2017;1514:93-101.

    Philips D, van den Braber M, Schumacher TN, Kvistborg P.

    Link to pubmed
 

Contact

  • Office manager

    Renske Muns-de Jong

  • E-mail

    rm.d.jong@nki.nl

  • Telephone Number

    0031 20 512 2055

Muns de Jong, Renske.jpg

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