Beginning with the patient: Dirk Elewaut shares his research inspiration

21 November 2017
A mixed group of VIB, VUB and UGent scientists led by Dirk Elewaut recently published a paper in the scientific journal Leukemia on their study of multiple myeloma, a type of cancer that affects bone marrow. Their groundbreaking results motivated us to ask Dirk to tell us more about the collaboration and the inspiration for his research.

As we age, our bone marrow is replaced by fat – increasing our risk of developing multiple myeloma. To find out why, Dirk Elewaut and his team at the VIB-UGent Inflammation Research Center investigated the role of
leptin, a hormone produced by fat, in reducing the anticancer immunity of natural killer T cells, known as NKT cells. Compounds exist today that selectively activate these cells, but stimulation causes NKT cells to go into
a dormant state called ‘anergy’ and no longer protect against cancer cells or pathogens for a period of time.
Using the myeloma model developed by Karen Vanderkerken and Eline Menu of VUB, the researchers boosted cancer protection by blocking the leptin receptor. Doing so restored NKT cells’ functioning when they would normally be in a state of anergy.

Their results could lead to new methods of treating other cancers that are influenced by the same mechanism.

As a medical doctor as well as a researcher, what inspires your research? Do your ideas stem from lab findings or from situations you encounter in your interactions with patients?
Dirk: “Our team tries to study human diseases as closely to the patient as possible. This approach implies that we begin by studying observations in patients, and then translate our observations to model systems to
study the immunobiology of the disease. This reverse approach makes it likely that our research questions are relevant to human disease. For this paper, we were struck by the discovery that bone marrow is gradually replaced by fat as we age. However, very little was known about how this impacts tumor immunity. Since this fat accumulation is associated with a greater risk for developing multiple myeloma, our goal was to clarify our
understanding of the underlying mechanisms.”

This research was performed in close collaboration with the VUB group of Karen Vanderkerken and Eline
Menu. When and how did this collaboration start?
Dirk: “We’ve been collaborating with Eline and Karin’s team for some time now. Initially, we tested the effects
of activating NKT cells in an experimental myeloma development setting. During this collaboration, we
came up with the idea for a joint project – which our ‘shared’ PhD student Mérédis Favreau started on five
years ago. As part of this project, we’ve been interacting with both the VIB teams as well as clinical hematology teams in Belgium and France, which led to this paper’s translational research story.”

The VIB-UGent group of Jan Tavernier was also involved. What was their role in this research?
Dirk: “Leptin and immunity have been the focal points of our long-term collaboration with Jan Tavernier (VIB-UGent Center for Medical Biotechnology). We discovered several years ago that leptin affects the functioning of NKT cells, and we tested several of the leptin receptor-neutralizing antibodies developed by his group. We have now extended our observations to include the modulation of anergy, or NKT cells’ dormant periods, which is a major drawback of stimulating them to be more active. By blocking the leptin receptor, we significantly reduced the effects of anergy on these cells, which led to superior antitumor effects.”

From a logistic point of view, collaborating across all these teams seems like a daunting task.
Dirk: “It sure was challenging: we had to align Belgian and French clinical hematologists who provided us with
clinical samples, our own NKT cell work in Ghent and the mouse model studies in Brussels. This required a very flexible researcher who had to be on the road a lot. And that’s where our PhD student Mérédis Favreau jumped in. Perfectly bilingual and connecting very well with all the teams, she was a vital link in this project.
On behalf of all VIB teams involved, I want to thank her again and wish her the best of luck in her new job in the pharma sector. I’m sure she will remember her VIB days vividly!”

Favreau et al., Leukemia 2017


Dirk Elewaut
©VIB-Ine Dehandschutter