Immuno-oncology took center stage in cancer research only recently. A more complete picture of the tumor microenvironment – the complex structures surrounding cancer cells – and technological evolutions offered scientists a deeper understanding of the human immune system's role in cancer development and in possible therapies. A few years ago, two researchers at the Universities of Brussels and Ghent decided to deep-dive into this promising cancer research field, each focusing on a specific angle.

In order to generate an anti-tumor response, our immune system should be able to recognize and target the cancer cells. This 'messenger' function is normally performed by our dendritic cells, a specific type of white blood cells. For a long time, researchers believed that tumors suppress these dendritic cells, impeding a proper immune response. In 2016, however, a team led by Professor Jo Van Ginderachter revealed that two specific types of dendritic cells – cDC1 and cDC2 – do resist suppression by tumors and have the power to cause an immune response. Damya Laoui was one of the team's main drivers.

Damya Laoui: "We surgically removed cDC1 and cDC2 from tumors in mice, boosted their activity and reinjected them as a vaccine. This strategy caused a strong anti-tumor response and slowed down the growth of the tumor – a gigantic breakthrough in immunotherapy for two reasons. On the one hand, we identified not one, but two dendritic cells able to cause an immune response. On the other, we found that these dendritic cells even have the potential to prevent cancers from spreading to other body parts – so-called metastasis – as they can remember the genetic print of the cancer cells."

"Following our success with mice experiments, we're now preparing clinical trials for humans. The idea is to 'vaccinate' cancer patients with dendritic cells taken from their own tumors in order to trigger their immune systems, kill cancer cells and slow down tumor growth. We should be careful with the term 'vaccine,' though, because we'll probably never be able to inject these types of dendritic cells into healthy people. Because we are reinforcing an individual's immune response, this technique can only succeed in people who are already dealing with a tumor. But the prospect of developing personalized therapies that offer a solution to metastasis and tumor relapse is very exciting."

While Damya Laoui is examining dendritic cells in Brussels, Lien Van Hoecke is doing the same in Ghent. As a member of the team led by Professor Xavier Saelens at the Center for Medical Biotechnology, she has been working on another possible cancer treatment stimulating the immune system. She was inspired by research in the area of personalized cancer therapies, such as the Pointillism project, but looked at it from a different angle.

Lien Van Hoecke: "Modifying the cells of a cancer patient is a viable strategy, but it costs considerable time and money to treat each person individually. That's why, during my PhD, I investigated a kind of 'one size fits all' approach. Previous research by Professor Peter Vandenabeele showed that necroptosis, a form of cell death, sounds an alarm for the immune system. This phenomenon is called immunogenic cell death and makes the dying cancer cells targets for the immune system, which remembers to seek out and attack those cancerous cells."

"We searched for a technique to provoke necroptosis and discovered that mRNA vaccines – a way to inject genetic information into the human body also used for the COVID-19 vaccines – can trigger this immunogenic cell death – activating the same dendritic cells Professor Laoui is investigating. mRNA methods are gaining attention in immuno-oncology because they provide highly adaptable platforms to feed tumors with genetic therapeutics. This offers us yet another promising route in fighting cancer."