New discovery could boost immunotherapy for mesothelioma patients

Early-career cancer researcher and recipient of several Cancer Council WA grants, Dr Nicola Principe, is investigating how cholesterol-lowering drugs could help make immunotherapy work better for people with mesothelioma. Dr Principe currently works at the National Centre for Asbestos Related Diseases and the University of Western Australia, and recently spoke to us about her research, what inspired her, and how Cancer Council WA funding has helped make this research possible.

Can you explain your research?

Immunotherapy is a standard treatment for many cancers, but unfortunately it doesn’t always work well for aggressive cancers like mesothelioma. My research is trying to improve immunotherapy by targeting cholesterol.

Our team have found that certain cholesterol-powered immune cells in the tumour, called regulatory cells, stop immunotherapy from working. So, we’re using cholesterol-lowering drugs, which are widely prescribed for other conditions, such as cardiovascular disease, to block those cells. So far in the lab we have found this is making immunotherapy more effective and helping to kill the cancer cells.

We’re working together with researchers and clinicians from Australian National Phenome Centre, Murdoch University, St Vincents Institute, Melbourne and Sir Charles Gairdner Hospital, to help with not only the methods of the research, but also how it will be clinically translated.

How did you come across this exciting discovery?

It actually started as a side project. We were doing genetic analysis and saw that genes associated with cholesterol were really highly expressed in regulatory cells from immunotherapy resistant tumours. Other researchers had noticed a similar pattern in regulatory cells, but no one had tested whether immunotherapy resistance was caused by cholesterol-powered regulatory cells. It was one of those weird, unexpected findings – even my supervisors didn’t believe it at first!

What stage is the research at now?

We’re still in the very early stages, so working mostly in the lab looking at immune cells and cancer cells and what energy they need to survive in the tumour environment. We also use coding and bioinformatics to study the genes that help these cells make proteins. This helps us understand what the cells are doing and how we can target them.

What are the biggest challenges with treating mesothelioma?

One of the biggest challenges with treating mesothelioma is that it has a long latency period. Patients are often exposed to asbestos decades before they show any symptoms, sometimes 40 to 50 years. By the time they’re diagnosed, the cancer is often very aggressive and hard to treat. That’s why this research has the potential to really impact treatments for mesothelioma patients.

Why is this approach so promising for patients?

The exciting part is that cholesterol inhibiting drugs are already approved and widely used to manage cholesterol. We know they’re safe, they’re easy for patients to take, and they don’t have many side effects. We hope that through this research, these drugs could be easily repurposed into the cancer clinic to help patients in the not-too-distant future.

Could this approach help other types of cancer too?

We hope so. These same regulatory cells seem to be involved in immunotherapy resistance in other cancers too. I’ve started expanding into lung cancer models, and there’s some evidence from other studies that cholesterol inhibitors could help there as well. It’s very exciting.

Why did you choose to go into cancer research?

I’ve had quite a few of my family and friends affected by cancer, including my mum, who passed away from a rare cancer. At the time, it felt like no one was doing anything about rare or aggressive cancers. That really drove me to this area. I still have the same passion I had in high school when I told my teachers I wanted to do cancer research, and I love that I get to do it here in WA.

What impact has Cancer Council WA funding had on your research?

It’s been huge. Cancer Council funding has allowed me to be here full time, build collaborations, and author two publications during the final years of my PhD when my other scholarship funding had ended. It also just really motivates me. Knowing the Cancer Council WA community is behind this work makes me want to push harder to make a real impact for people affected by cancer.