Prospective and genetic analyses implicate lower immunosurveillance in the aetiology of prostate cancer

Tumour-promoting inflammation and immune evasion are key features of cancer, but prospective evidence linking specific immune pathways to prostate cancer risk remains limited. Here we show that circulating proteins involved in immune regulation may influence prostate cancer development. We analyse 368 immune- and inflammation-related proteins measured in blood samples from men in the European Prospective Investigation into Cancer and Nutrition (EPIC), including 1434 cases and matched controls, and combine these results with data from UK Biobank. While no proteins are associated with risk in EPIC alone after multiple testing correction, meta-analysis identifies several proteins linked to prostate cancer risk, including IL15 and FLT3LG, in particular, in blood taken long before diagnosis. Higher levels of immune surveillance-related proteins, particularly those involved in natural killer and T cell activity, are associated with lower prostate cancer risk, whereas genetic evidence implicates PARP1, SPINT2 and NME3 in increased risk. These findings suggest that immune pathways play a role in prostate cancer development and highlight potential targets for prevention.