How breast cancer escapes the immune system

Our immune system is one of the most powerful, adaptable and trainable networks in our body. It protects us every day against viruses and bacteria, and in principle, it can also recognize and destroy cancer cells. Yet tumours find ways to slip past it. 'If we understand how they do that, we can find new and more effective ways to treat breast cancer.'

Immunotherapy is currently given largely as a “one size fits all” treatment, and only some patients benefit. One reason, Karin explains, is that breast cancer varies greatly from patient to patient, including which immune cells are present and how well they work. 

'We found that the genetic make-up of a breast tumour strongly shapes which immune cells it attracts, how those cells are activated, and whether the tumour responds to immunotherapy. Understanding these mechanisms in detail is how we move towards personalized immunotherapy.'

Making immunotherapy more personal

'I hope our work will make immunotherapy more personal, so that each patient receives the treatment that fits the biology of their tumour and their immune system.'

'This is especially important for patients with metastatic breast cancer, which is currently incurable,' Karin continues. 'When cancer cells spread to other organs, they meet different immune cells in each location. Our goal is for these patients, too, to receive effective (immuno)therapy.'

Following the unexpected

Some of the most important findings started with something the team wasn’t looking for: an unexpected but clear observation that led them in a new direction.

One example came from Karin’s long-term collaboration with NKI clinician Marleen Kok. 'We profiled the blood of breast cancer patients in great detail, before and during immunotherapy. We wanted to learn what makes patients who respond different from those who don’t, so that one day we might turn non-responders into responders. Because these patient samples were so precious, we analyzed them very deeply.'

They were particularly interested in one immune cell type, neutrophils, but saw no difference between patients who responded and those who didn’t. Instead, another cell type stood out: eosinophils. These cells have long been overlooked in cancer research, and they found that their numbers increased in patients who responded to treatment. 

'We hadn’t set out to study them, but we decided to follow up on this finding in the lab. They turned out to be very important for the response to immunotherapy.' 

They now have a dedicated research line to understand eosinophils better. The ultimate aim is to harness them therapeutically and improve how breast cancer responds to immunotherapy. 

'It taught me to always keep an eye open for what you’re not looking for.'