Immunotherapy has transformed cancer treatment, offering new hope for many patients. Yet not every patient benefits equally. Some immune cells are remarkably effective at recognising and destroying cancer cells, while others gradually lose their ability to respond once they reach the tumour environment.
Understanding why these differences exist is one of today's biggest challenges in cancer research. Two collaborative projects supported through the Oncode Synergy Projects 2026 programme are tackling this question from complementary perspectives. By combining expertise across the Oncode community, these collaborations aim to uncover new insights that could contribute to more effective immunotherapies.
What makes some immune cells exceptional?
Some T cells appear to be natural experts at eliminating cancer. In the project Illuminating super engager T cells: A microscopy study spanning cellular and molecular scales, Oncode researchers Megan Farrell and Jessica Mazalo are investigating a rare group of T cells known as super engagers.
Earlier research showed that these cells behave differently from other T cells. Rather than attacking individual cancer cells, they surround tumours and spread across multiple cells, causing widespread tumour damage. What makes these immune cells so effective, however, remains unknown.
To answer this question, the researchers will combine advanced microscopy technologies developed at their respective institutes to visualise these cells at the molecular level. By uncovering the mechanisms behind this remarkable behaviour, they hope to identify new strategies that could inspire future cancer immunotherapies.
Why do some T cells stop fighting cancer?
While one collaboration focuses on highly effective immune cells, the second investigates the opposite challenge.
In the project Decoding signaling networks that regulate dysfunctional T-cell states in cancer, Oncode researchers Kaspar Bresser, Nila Servaas, Kathy Jastrzebski and Bram Thijssen are studying why T cells become dysfunctional, or "exhausted", after entering the tumour environment. Once this happens, their ability to eliminate cancer cells is greatly reduced, limiting the effectiveness of immunotherapy.
Using the newly developed single-cell (phospho)protein prolifing P2-seq technology together with CRISPR, the team will measure signalling activity in individual T cells while selectively switching off specific genes. This will allow the researchers to identify the molecular pathways that regulate T cell dysfunction and reveal potential targets for restoring immune activity.
Although the two projects explore different biological questions, they share a common goal: understanding how immune cells recognise, attack and respond to cancer. Together, they demonstrate how collaborative research can help answer complex scientific questions and support the development of more effective immunotherapies for patients.
What the researchers say
Meet the researchers behind these collaborations and discover what excites them most about their projects.
Illuminating super engager T cells: A microscopy study spanning cellular and molecular scales
Megan Farrell
“This small cohort of immune cells hold so much potential as they are primed to be highly effective at killing cancer. I am excited to work together with Jessica Mazalo to understand what makes these cells so special by visualizing them in action using our combined advanced microscopy approaches.”
Jessica Mazalo
“This exciting venture will enable us to probe the molecular processes behind an elusive T cell anti-tumour behaviour in a creative and technologically innovative manner. I’m thrilled to be partnering with single molecule imaging expert Megan Farrell to push the boundaries in this new imaging pipeline.”
Decoding signaling networks that regulate dysfunctional T-cell states in cancer
Kaspar Bresser
“There are still many unknowns about defective T cell responses in cancer. This project allows us to investigate an underexplored piece of this puzzle. I look forward to uncovering insights that may help restore T cell function and improve cancer treatment.”
Nila Servaas
“I am excited to address how T cell signaling is rewired in cancer. Applying this new single-cell technique really offers a unique opportunity to move beyond descriptive studies and identify actionable mechanisms underlying T cell dysfunction. Hopefully this will uncover mechanisms that can inform improved immunotherapy for cancer patients.”
Kathy Jastrzebski
“I’m excited to work with the talented team we’ve put together, combining expertise that allows us to apply cutting-edge single-cell technology to understand the intracellular signaling underlying T cell dysfunction. Hopefully, the insights this work uncovers will help improve immunotherapy outcomes for patients.”
Bram Thijssen
“It is exciting to apply a new experimental technique that has been in the works for a long time, to a new relevant problem. We can’t wait to see what it will tell us about dysfunctional T cells.”
About the Oncode Synergy Projects 2026
Inside the Synergy Projects 2026 is a series highlighting the collaborative research projects supported through the Oncode Synergy Projects 2026 programme. Supported through the collaboration between Alpe d'HuZes, KWF and Oncode Institute, the programme brings together Oncode researchers from different institutes and disciplines to develop innovative approaches to cancer research.