Immune cells breakthrough raises hopes for delaying treatment resistance

New research funded by Prostate Cancer UK has found that the immune system could play a role in advanced prostate cancer becoming resistant to hormone therapy.

This exciting new discovery could change the way that we view treatment resistance and raises the possibility of reversing this process.

Hormone therapy is the main treatment for men diagnosed with advanced prostate cancer, where the cancer is starved of hormones like testosterone to prevent it growing. However, the cancer eventually becomes resistant and finds a way to start growing again.

Until now, most research into treatment resistance has been focussed on genetic mutations in the cancer. These mutations do have a very important role, but this new research published in the prestigious journal Nature suggests that it is not the whole story and resistance could be triggered by other cells around the cancer.

The researchers, based in London and Switzerland, studied the effects of immune cells called myeloid-derived suppressor cells (MDSCs, shown in green in the image above), which can penetrate the tumour. They had found that samples of prostate cancer that are resistant to hormone therapy contain more of these MDSCs, so we funded the team to study the effect of stopping these cells thanks to the generosity of our supporters and the Barry Family Foundation. They discovered that blocking these MDSCs could delay or prevent treatment resistance in mice.

Drug to prevent growth trigger already exists

Looking more closely, the researchers discovered that this effect was due to a specific protein called IL-23 that is produced by the MDSCs. This protein has a similar effect to testosterone and triggers the cancer to start growing despite the hormone therapy.

Fortunately, a drug that stops IL-23 already exists. It is used to treat conditions where the immune system is overactive, like the skin condition psoriasis. Our research grant will now allow the researchers to set up a trial to test this idea in men with prostate cancer for the first time.

Professor Johann de Bono, from The Institute of Cancer Research, London, said: “Our study found an important interaction between hormone signalling and the immune system. We believe we could exploit this to reverse hormone resistance in prostate cancer, and boost the effect of widely used prostate cancer drugs such as enzalutamide.

“We are keen to start clinical trials to investigate how we can combine this new form of immunotherapy with existing hormone therapies, to improve treatment for men with advanced prostate cancer.”

A completely new approach to treating men

It’s difficult to say at this stage how well this will work in men with advanced prostate cancer. However, even a small delay in the development of treatment resistance could have a big impact for men facing an incurable disease.

Dr Matthew Hobbs, our deputy director of research, commented:“Treatments that try to activate the immune system have had significant success in many types of cancer, but so far this approach has only been successful in very small numbers of men with prostate cancer.

“We funded the study released today to find out whether targeting a different type of immune cell could reverse the process that eventually makes prostate cancers resistant to current treatments. It could offer a completely new approach to treating the disease. This investigation is at an early stage and we are also funding the crucial next stage still which is to test this new approach in men.”

This new research shows the importance of looking at the surrounding environment of the cancer, instead of only studying the cancer cells themselves. This is exactly the kind of impact we wanted to make when we funded this project through a Research Innovation Award in 2016. It’s thanks to the generous contributions from our supporters that we’re able to fund such ground-breaking research and it’s fantastic to see it paying off already.

Treatments targeting the immune system have had some significant successes in other cancers, but to date has only worked in very few men with prostate cancer. Earlier this week, Prostate Cancer UK held our first Immunology Frontier Meeting, gathering world experts to meet and discuss the key issues that we need to overcome to make good use of the exciting opportunities that these new types of treatment present. With your continued support, discoveries like this will help to stop prostate cancer being a killer.

(Image credit: Prof. Johann de Bono)