Department Radiotherapy research efforts

Ambition and impact

We develop predictive profiles based on micro-environmental tumor characteristics. This way, we expect to better be able to guide treatment selection and optimization for patients on an individual basis.

Our experimental and clinical research is aimed at molecular immunology and vascular architecture & microenvironmental parameters, but also additional topics like EGFR.

Molecular Immunology

Dendritic cells (DC) are the professional antigen presenting cells (APC) of our immune system. They are able to initiate immune responses against pathogens or tumors, but also have the capacity to prevent (auto)-immune responses harmful to the host. My research is centered around the molecular and functional analysis of DC in mouse and man. Applying different molecular approaches at the genomic and proteomic level a set of novel DC-antigens have been identified, including chemokines (DC-CK1, CXCL16), a novel multiple membrane spanning receptor (DC-STAMP), a transcription regulator (DC-SCRIPT). Knowledge regarding DC-immuno-biology is essential for the development and design of DC-based vaccines in mouse models as well as in clinical studies in cancer patients. More recently, regulatory T cells that are crucially involved in balancing the immune system are studied at the molecular and functional level as well as in immunotherapy of cancer.

Vascular architecture and microenvironmental parameters

An important objective is the development of predictive profiles based on Vascular Architecture and Microenvironmental Parameters (VAMP). The ultimate goal is to provide a mechanistic basis for the optimization of treatments that combine radiotherapy with novel biological modifiers and for the development of patient selection strategies.
 

Other topics we focus on

• analyzing EGFR signaling related to radiation resistance (PI3-K/AKT pathway related to tumor vasculature)
• proliferation and hypoxia involvement
• non-invasive imaging of the tumor microenvironment (vasculature, hypoxia, proliferation and the EGFR)
• assessment of endogenous markers related to tumor cell metabolism (lactate, monocarboxylate transporters etcetera)

Furthermore, clinical therapy could be much improved when the knowledge gathered in fundamental immunological studies is translated into clinical immunotherapy studies. In this light, our research interests focuses on the molecular analysis of professional antigen presenting dendritic cells and Myeloid and T-regulatory cells, and their function in the immune system in health and disease.

• Techniques

  The biology of tumors is studied at the macroscopic (PET) and microscopic (cell, subcellular) level. The aim is to compare different functional imaging modalities for the same tumor.
  The focus is on:

  • Quantitative immunohistochemistry
  • Cell culture systems
  • Molecular Immunology

  Quantitative immunohistochemistry

  The backbone of this system are:

  • The vascular architecture (9F1 or CD31/24)
  • Tumor blood perfusion (Hoechst 33342)
  • Exogeneous markers/indicators of hypoxia (CA-IX, pimonidazole)

  This system can be extended by:

  • Proliferation (BrdUrd, IdUrd, Ki67)
  • Growth factors ((p)EGFR, (p)AKT)
  • DNA damage (gamma-H2AX, 53BP1)

  At the microscopic level, the tumor biology is studied in a quantitative manner with preservation of the tissue architecture and spatial associations. Therefore, we have developed a system for co-registration and quantitative analysis of micro-environmental phenotypic tumor characteristics. The method is based on immune-histochemical detection of multiple fluorescent signals in complete tissue sections.

  Quantification

  Components of our digital imaging systems: 

  • Multi-color fluorescence microscopy
  • Computer-controlled scanning and imaging system:
    • CCD camera
    • Motorized scanning stage
    • Image acquisition and analysis software

  Cell culture systems

  Our laboratory has permission for genetically modified organisms ('ML-II').

  The facilities are:

  • Western Blotting
  • Isolation of RNA and DNA
  • Horizontal gel electrophoreses
  • Incubations at 0.1-20% oxygen (Hypoxystation)