Researchers funded by Cancer Research UK have found clues in the blood that could lead to new ways of preventing prostate cancer. 

In a study of more than 20,000 men, a team at Oxford Population Health found that higher levels of certain immune-activating proteins were associated with a lower prostate cancer risk. 

Previously, scientists suspected that prostate cancers could completely suppress the body’s immune defences, but these findings suggest that the reality is more complicated. It now appears that, in some men, the immune system can help clear out abnormal prostate cells before they develop into cancer – effectively stopping the disease before it has the chance to start.

“Prostate cancer had been considered immunologically ‘cold’ ‒ unlikely to trigger a strong immune response,” explained Dr Mahboubeh Parsaeian, the lead author of the study, “but we normally study the immune system after the tumour is already there. Our findings suggest that the immune system does, in fact, play a role in the early development or suppression of prostate cancer.” 

This points to the possibility that treatments designed to boost the immune system could become targeted tools for preventing prostate cancer 

“The associations we found cannot give us a complete understanding of the underlying biology ‒ how these proteins act, and interact, during cancer development ‒ but they do suggest that existing drugs which manipulate these pathways could offer a way of intervening while men are still healthy, rather than treating the disease after diagnosis,” said Parsaeian.

Finding signals in the blood

This study, published today in Nature Communications, is the largest of its kind to investigate connections between the immune system and prostate cancer risk. 

The researchers combined two different data sources for the project. First, they analysed blood samples from the European Prospective Investigation into Cancer and Nutrition (EPIC), comparing levels of 368 immune and inflammation-related proteins in 1,434 men who developed prostate cancer (on average more than a decade later) with a matched group of 1,434 men who did not.

Alongside EPIC, the team analysed data from 21,481 male participants in UK Biobank, including 1,147 people with prostate cancer. Here, the researchers used genetic tests to investigate whether the proteins they identified were likely to have a direct effect on prostate cancer risk.

There were multiple hits. One of the strongest findings involved interleukin-15 (IL-15), which stimulates and maintains cancer-fighting T cells and natural killer cells. Across the combined analyses, higher levels of IL-15 were associated with a 14% lower risk of prostate cancer after seven or more years. In the EPIC cohort, where information on tumour characteristics was available, higher IL-15 was also associated with a 26% lower risk of advanced prostate cancer.   

Several other immune-related proteins showed similar associations, and the study also identified a separate potential route involving PARP1, a well-known DNA-repair protein.  

Using genetic data, researchers found that men with genes linked to higher PARP1 levels had an increased risk of prostate cancer. PARP inhibitors such as olaparib are already used to treat some prostate cancers, particularly tumours with defects in DNA repair pathways such as BRCA1 or BRCA2, but they aren’t currently used for cancer prevention.  

Professor Karl Smith-Byrne, one of the lead researchers at Oxford Population Health, highlighted what the research could mean going forward. 

“What’s striking in our study is that the strongest immune signals were present more than seven years before diagnosis, pointing to a much earlier period when the immune system may be helping to keep abnormal cells under control,” he said.  

“IL-15 is particularly interesting because it supports natural killer cells and killer T cells, which are precisely the cells we would expect to participate in this kind of surveillance for abnormal cells. And the PARP1 finding raises a striking possibility: that a pathway already targeted after prostate cancer develops might also influence whether the disease develops in the first place.” 

Next steps for preventing prostate cancer

The next step is to test whether it’s possible to influence these immune-boosting and DNA repair proteins to safely lower men’s prostate cancer risk. That will happen through Cancer Research UK’s Prostate Cancer Aetiology and Prevention (PCAP) programme, which we set up to find ways of preventing prostate cancer before it’s diagnosed. 

“These richly characterised population studies are transforming our understanding of cancer,” said Professor Ruth Travis, one of the lead researchers on PCAP. “For the first time, they allow us to examine the biology of the disease years before it is diagnosed.  

“By analysing thousands of proteins, we’re uncovering new clues about the mechanisms that influence who develops prostate cancer and who does not. These insights could help us move towards more effective prevention strategies, and identify the critical windows during which intervention may have the greatest impact.”