Thesis defense: 24-02-2023
Promotor: Prof.dr. M. Ritt, prof.dr. S. Gibbs. Copromotor: Dr. F.B. Niessen
Thesis defense: 24-02-2023
Promotor: prof. dr. H.E. de Vries, prof. dr. W.M. van der Flier. Copromotor: prof. dr. Ir. C.E. Teunissen, dr. M. E. Witte
Thesis defense: 26-01-2023
Promotor: prof. dr. R. Mebius, prof. dr. M. van Egmond. Copromotor: dr. M. E. Witte
Thesis defense: 14-12-2022
Promotor: prof. dr. Y. van Kooyk, prof. dr. T.D. de Gruijl. Copromotor: prof. dr. J.J. van der Vliet
Thesis defense: 27-10-2022
Promotor: prof. dr. M. van Egmond. Copromotor: dr. S.J. Oosterling
Thesis defense: 21-10-2022
Promotores: prof. dr. H. E. de Vries, prof. dr. M. P. J. de Winther. Copromotor: dr. ir. J. Van den Bossche
Thesis defense: 21-4-2022
Promotor: prof. dr. H.E. de Vries. Co-pormotor: dr. G. Kooij
Febe van Maldegem is assistant professor and group leader in the Department of Molecular Cell Biology & Immunology. Her work focusses on the complex role of the tumour microenvironment in non-small cell lung cancer (NSCLC), crucial for mediating anti-tumour immunity, but more frequently imposing resistance to therapy. Key to her work is the use of highly multiplex technologies, such as Imaging Mass Cytometry with which the tumour microenvironment can be studied in great detail, revealing the activation states as well as the spatial context of the many cells within the tissue. Febe van Maldegem’s research program, financially supported by the Amsterdam UMC fellowship, the Paulien van Deutekom foundation, the European Committee (under the EU Horizon program), KWF and NWO, aims to improve therapeutic options for patients with non-small cell lung cancer by rationalising the design of combination, mindful of the important role for the tumour microenvironment in determining success.
To understand how we can manipulate the tumour microenvironment (TME) to benefit therapeutic strategies, we will first need to better understand this complex system. This research line asks the basic questions: How does the TME evolve over time during tumour development, and what are the selective forces that drive this evolution? A key project within this research line is the EU funded Horizon Mission Cancer project “SPACETIME” (spacetimeproject.eu): In several in vivo models for non-small cell lung cancer, as well as in patient samples from routine diagnostics, we study the spatial TME composition, from tumour onset into progressive disease. The resulting spatial TME profiles will be used to develop predictive and prognostic biomarkers and to design novel therapeutic targets aimed at disrupting or enhancing cellular interactions. One of the key technologies that we use to characterise the spatial TME used is Imaging Mass Cytometry, with which the tumour microenvironment can be studied in great detail, revealing the activation states as well as the spatial context of the many cells within the tissue.
Video, sequentially highlighting 15 out of the 27 markers this small lung tumour was stained for using Imaging Mass Cytometry (CX3CR1, PECAM, aSMA, EPCAM, B220, CD103, LY6G, CD8, CD4, CD11c, CD68, F480, CD45, CD44, MHC-II)
Rationally combining chemoradiotherapy with immune checkpoint inhibitors (ICI)
Neoadjuvant (chemo)radiotherapy (CRT) is the current standard of care for low grade NSCLC, but the field is moving towards combinations with ICI. Chemotherapy and radiotherapy can benefit immune responses by inducing immunogenic cell death, but can also be toxic to the immune cells. We will assess the impact of this treatment combination by analysing patient samples from clinical trials, in collaboration with the VUmc, comparing different combinations of these therapies in pre- and post-treatment biopsies. In vitro and pre-clinical studies will be used to optimise the treatment dosing and scheduling, to provide a rational basis for design of the next generation of clinical trials. Predictive biomarker development for response to therapy is another key aim of this research line.
Spatial multiplex analysis of lung cancer reveals that regulatory T cells attenuate KRAS-G12C inhibitor-induced immune responses. Cole M, Anastasiou P, Lee C, Yu X, deCastro A, Roelink J, Moore C, Mugarza E, Jones M, Valand K, Rana S, Colliver E, Angelova M, Enfield K, Magness A, Mullokandov A, Kelly G, Gruijl T, Molina-Arcas M, Swanton C, Downward J, van Maldegem F. Science Advances. 2024 Nov;10(44).
A Single-Arm Trial of Neoadjuvant Ipilimumab Plus Nivolumab With ChemoRadiotherapy in Patients With Resectable and Borderline Resectable Lung Cancer: The INCREASE Study. Bahce I, Dickhoff C, Schneiders FL, Veltman, JL, Heineman DJ, Hashemi SMS, Vrijmoet AB, Houda I, Ulas EB, Bakker J, van de Ven P, Bouwhuis N, Meijboom LJ, Oprea-Lager DE, van Maldegem F, Fransen MF, de Gruijl TD, Radonic T, Senan S. Journal for ImmunoTherapy of Cancer 2024 Sep 30;12(9).
Imaging mass cytometry in preclinical studies of lung cancer. F. van Maldegem Book chapter in “Revealing Uncharted Biology With Single Cell Multiplex Proteomic Technologies”, Elsevier, edited by W. Fantl. 2024 Jun 25
Therapeutic KRASG12C inhibition drives effective interferon-mediated anti-tumour immunity in immunogenic lung cancers. Mugarza E*, van Maldegem F*, Boumelha J*, Moore C, Rana S, Sopena ML, East P, Ambler R, Anastasiou P, Clavijo PR, Valand K, Cole M, Molina-Arcas M, Downward J. Science Advances, 2022 July 22;8. doi: 10.1126/sciadv.abm8780
Characterisation of tumour microenvironment remodelling following oncogene inhibition in preclinical studies with imaging mass cytometry. Van Maldegem F, Valand K, Cole M, Patel H, Angelova M, Rana S, Colliver E, Enfield K, Bah N, Tsang VSK, Mugarza E, Moore C, Hobson P, Levi D, Molina-Arcas M, Swanton C, Downward J. Nature Communications. 2021 Oct 8;12.
Joelle van Elk
Technician
For all groups within our department (Department of Molecular Cell Biology & Immunology) I support all the research that involves in vivo work.
Maud Reugebrink, MSc
PhD student
My research focuses on understanding the dynamics of tumor-specific T cell responses during progression of non-small cell lung cancer. Using both patient samples and mouse models, I study how (tumor-specific) T cell clonotypes are spatially distributed across tumor, blood, and lymph nodes during tumor evolution, and how these patterns relate to their functional characteristics. The aim is to better understand the timing and location of anti-tumor T cell activity and identify mechanisms of immune activation and resistance.
Meggy Verdonschot
Technician
The projects I am working on are focused on spatial and phenotypic characterization of the tumor microenvironment in non-small cell lung cancer using Imaging Mass Cytometry to gain more insight into the tumor evolution and the effect of different therapies.
Sofie Koomen, MSc
PhD student
The focus of my research is rationalizing and optimizing the combination of (chemo)radiotherapy and immunotherapy for the treatment of non-small cell lung cancer. For this, it will be crucial to enhance our knowledge about the effect of the therapies on the cells infiltrating the tumor microenvironment and their spatial context – and vice versa. Imaging Mass Cytometry will provide this in depth spatial and phenotypic characterization of the components of the tumor microenvironment.
Susan van Hal
Technician
I support the lab with all in vivo and ex vivo experiments for the projects and mainly the SPACETIME consortium. I am also supporting the group with organization and provide hands-on help where needed.
Wies Vallentgoed, MSc
Postdoc
My research focuses on the spatio-temporal evolution of the tumour microenvironment in KRAS-mutant and oncogenic driver-negative lung adenocarcinoma. To uncover the biological processes underlying progression and therapy resistance, I investigate the co-evolution of the tumour and immune responses. Imaging Mass Cytometry, in addition to other spatial-omics techniques, provides detailed spatial characterization of the key components of the tumour microenvironment. By analysing patient biopsies from stage 0 to metastatic disease, complemented with mouse models to study early developments post-tumour initiation, I will examine the spatial signatures of tumour-host interactions in an evolutionary context
Xiaofei Yu, MSc
PhD student
My works focuses on the evolution of tumor microenvironment. I investigate the changes in TME composition from early time points to advanced stages and under different experimental conditions with in vivo models. Imaging Mass Cytometry will provide detailed phenotypic and spatial characteristic of the cellular relationships in the tissue.
Thesis defense: 1-7-2021
Promotores: prof. dr. M. van Egmond, prof. dr. R. Mebius
Thesis defense: 29-6-2021
Promotor: prof. dr. Y. van Kooyk. Copromotor: dr. J.J. Garcia Vallejo