The best ideas often start with good questions. Experiments start with a why, and breakthroughs are often sparked by a what if.
For example: Why do immunotherapies – treatments that harness our own immune system to fight cancer – work remarkably well in some patients, but not in others? And what if we could change that?
A new research team, supported by a $3-million Terry Fox New Frontiers Program Project Grant (PPG), is determined to find answers.
Using advanced technologies and animal models, the team will explore how the immune system, nervous system and gut microbiome interact in the context of cancer. By looking at this bigger picture, they aim to identify what’s going wrong and how the entire body can be better empowered to eliminate cancer through more personalized, targeted treatment strategies.
“To my knowledge, this is the first time anyone has looked at how these three systems work together,” says Dr. Michele Ardolino, senior scientist at the Ottawa Hospital Research Institute, professor at the University of Ottawa and the project’s lead investigator. “This kind of collaborative effort is only possible through a mechanism like the Terry Fox New Frontiers Program Project Grant.”
The team’s core idea is simple but bold: to truly understand why some patients don’t respond to immunotherapy, we need to stop looking at body systems in isolation – or even just in pairs. Instead, we need to understand how they all work together, as a coordinated team.
From napkin sketch to New Frontiers Program Project Grant
Like many great ideas, this one began with a conversation – a casual chat among experts at a research conference. Dr. Ardolino along with Drs. Nicolas Jacquelot and Kathy McCoy (University of Calgary) and Sebastien Talbot (Queen’s University) were serendipitously at the same table, optimistic about how their research had an impact in cancer immunotherapy but frustrated by how hard it is to connect different fields in a more holistic manner. This challenge became an opportunity – and a what if – which became a bold plan scribbled on the back of a napkin.
What if the key to overcoming resistance to immunotherapy isn’t in the immune system alone, but in the way the immune, nervous and microbial systems interact?
That napkin sketch became a collaborative, cross-disciplinary research proposal – that recruited even more researchers including Dr. Sebastien Talbot (Queen’s University) – and then a successful grant with the potential to transform cancer treatment.
A new approach to immunotherapy resistance
Past research from members of the team has shown that by stimulating different systems, previously resistant tumours can be made sensitive to treatment. This insight underpins the new approach.
“Our idea, which is a little different from conventional thinking, is that these patients are not inherently resistant,” explains Dr. Ardolino. “It's just that we haven’t figured out how to make them sensitive to the drugs we already have.”
If the team can uncover what’s blocking the immune system, whether it is nervous system signalling or a microbial imbalance, they can help lay the foundation for new therapies.
“We can better understand how the immune system works only when it doesn’t work very well, and cancer is a prime example of that. By unravelling this mystery, we hope to turn that knowledge into better treatments.”
Finishing it, together
This is a high-risk, high-reward project that required a bold idea and an ambitious team of experts to match. For Dr. Ardolino, this award represents more than just funding.
“There’s a sense of community that comes with this award because you become part of the Terry Fox research community, which is recognized internationally for the excellence of its work. I’m proud and excited to be part of that,” he says.
“This is exactly the kind of science that Terry Fox himself embodied: pushing beyond conventional boundaries to achieve something extraordinary. With Terry Fox funding, we're not just conducting research. We are pioneering an entirely new way to understand and treat cancer.”