Tineke Lenstra and Daniela Thommen receive Vidi grant

Using the advanced methods they have been developing and refining over the past years, they will be peeking into individual human cells and studying the ‘social’ environment of immune cells in tumors. The Netherlands Organisation for Scientific Research (NWO) awards Vidi grants to experienced scientists doing innovative research.

Both Daniela Thommen and Tineke Lenstra have a strong drive to better understand what is going on within human cells and tissues. What goes wrong once cancer comes into play? Tineke is looking for answers inside single cells, whereas Daniela zooms in on the context of immune cells and their (in)ability to fight cancer cells.

Insight into the cell

"How do cells manage to switch on the right genes at the right time, and exactly as long as they need?" Tineke Lenstra wonders. Genes that are switched on create messenger substances that ultimately determine the behavior and fate of cells. "The button that switches a gene on, as it were, switches off again after ten seconds, but the gene still remains active for ten more minutes. How does that work? Once we have a solid grasp on that, we can gain an understanding of where this goes wrong in cancer cells."

But Lenstra won’t find her answers unless she goes off the beaten track. "Most experiments analyze groups of cells and their average activities. But if you zoom in further, you quickly discover that every cell displays its own distinct behavior. That's why you have to study the individual cells." And that’s what she does, using advanced microscopes. Using techniques she developed herself, they allow her to look into the cells with great detail and follow the individual molecules over time. This grant will give her the opportunity to start investigating this process in human cells over the coming years.

Geographic map

The fact that the surroundings of cells are at least as important as their interior, is becoming more and more clear to fellow group leader Thommen. She has come up with a technique for studying miniature tumors in the lab. “In contrast to other technologies, our platform allows us to not only study which cells are present in a tumor and where exactly they are located, but also what they do and how they respond to therapy. This makes it very powerful.”

She will be working on a huge outstanding question: why do some cancer patients respond to immunotherapy and others don’t? “We know that immune cells called T-cells have the potential to fight cancer. But sometimes they just don’t. Tumors resemble geographic maps with different areas. Therefore, I’m trying to understand how the surroundings of these immune cells affect their activity. Do they need to be in a specific location, for example, in order to do their jobs? Or do they need to communicate with specific other cells?” The answers to these questions will help us improve immunotherapy for patients.